Spectrum and prevalence of BRCA1/2 germline mutations in Pakistani breast cancer patients: results from a large comprehensive study

Rashid, Muhammad Usman; Muhammad, Noor; Naeemi, Humaira; Khan, Faiz Ali; Hassan, Mariam; Faisal, Saima; Gull, Sidra; Amin, Asim; Loya, Asif; Hamann, Ute

doi:10.1186/s13053-019-0125-5

Hereditary Cancer in Clinical Practice

Table 2 Deleterious BRCA1/2 germline mutations in Pakistani breast/ovarian cancer families

From: Spectrum and prevalence of BRCA1/2 germline mutations in Pakistani breast cancer patients: results from a large comprehensive study

Family	Exon	BIC designation			HGVS designation		Mutation type^b	Reported in databases (No. of entries)^c
Family	Exon	Nucleotide	Codon	Designation	Nucleotide change^a	Effect on protein	Mutation type^b	Reported in databases (No. of entries)^c
BRCA1-small-range mutations
432	2	185	23	185insA	c.66dup	p.(Glu23Argfs*18)	FS	BIC (32)^d
723	2	185	23	185delAG	c.68_69del	p.(Glu23Valfs*17)	FS	BIC (2036)^d
372	Intron 4	IVS4-2	-	IVS4-2A>G	c.135-2A>G	Splice site	SP	BIC (1)
254^e	7	454	112	454delA	c.335del	p.(Asn112Ilefs*7)	FS	ClinVar (2)
449	7	509	130	Y130X	c.390C>G	p.(Tyr130*)	NS	LOVD (3)
296, 317, 340^e, 511, 521, 626^e, 747	11	804	229	804delT	c.685del	p.(Ser229Leufs*5)	FS	BIC (2)
470^e	11	903	262	Q262X	c.784C>T	p.(Gln262*)	NS	ClinVar (3)
711	11	1014	299	1014delGT	c.895_896del	p.(Val299Argfs*4)	FS	BIC (2)
669^e	11	1127	336	1127delA	c.1008del	p.(Glu337Lysfs*4)	FS	No^d
748	11	1307	396	1307delT	c.1188del	p.(Asp396Glufs*14)	FS	LOVD (1)
241^e	11	1309	397	1309delA	c.1190del	p.(Asp397Alafs*13)	FS	ClinVar (3)
722	11	1518	485	1518_1572dup55	c.1399_1453dup	p.(Ala485Glufs*13)	FS	No
336^e	11	1590	491	Q491X	c.1471C>T	p.(Gln491*)	NS	BIC (4)^d
N12	11	1898	593	1898delTATGGAA	c.1779_1785del	p.(Met594Serfs*3)	FS	LOVD (2)
N28, 328^e, 557^e	11	1912	598	L598X	c.1793T>G	p.(Leu598*)	NS	BIC (1)^d
574^e	11	2080	655	2080insA	c.1961dup	p.(Tyr655Valfs*18)	FS	BIC (13)^d
488^e	11	2268	717	E717X	c.2149G>T	p.(Glu717*)	NS	ClinVar (2)
236^e, 283^e, 489^e, 493^e, 593	11	2388	757	2388delG	c.2269del	p.(Val757Phefs*8)	FS	BIC (10)^d
363	11	2433	772	2433delGT	c.2314_2315del	p.(Val772Thrfs*4)	FS	LOVD (2)
550^h	11	2457	780	Q780X	c.2338C>T	p.(Gln780*)	NS	BIC (36)
362, 469	11	2459	780	2459delGGAA	c.2340_2343del	p.(Glu781Valfs*10)	FS	LOVD (2)
421^e, 442, 510^e, 542, 619^e	11	2524	802	2524delTG	c.2405_2406del	p.(Val802Glufs*7)	FS	BIC (5)^d
N34	11	2657	846	2657delAAT-insG	c.2538_2540delinsG	p.(Met847Glyfs*4)	FS	LOVD (2)
415^e, 660^e	11	2722	868	S868X	c.2603C>G	p.(Ser868*)	NS	BIC (11)^d
411^e	11	3090	991	K991X	c.2971A>T	p.(Lys991*)	NS	ClinVar (2)
247^e	11	3100	994	3100delGT	c.2981_2982del	p.(Cys994*)	FS	ClinVar (5)
299	11	3248	1043	3248delTATTAATGAA	c.3129_3138del	p.(Asn1043Lysfs*2)	FS	ClinVar (3)
N13^e, 399^e	11	3458	1113	3458delTGA	c.3339_3341del	p.(Tyr1113*)	FS	ClinVar (2)
610	11	3531	1138	G1138X	c.3412G>T	p.(Gly1138*)	NS	ClinVar (3)
N25	11	3596	1159	3596delAAAG	c.3477_3480del	p.(Ile1159Metfs*50)	FS	BIC (3)
279^e, 445^e	11	3717	1200	Q1200X	c.3598C>T	p.(Gln1200*)	NS	BIC (21)^d
382	11	3726	1203	R1203X	c.3607C>T	p.(Arg1203*)	NS	BIC (36)
646	11	3819	1234	3819delGTAAA	c.3700_3704del	p.(Val1234Glnfs*8)	FS	BIC (61)
210^e, 211^e, 313^e, 316, 332^e, 463, 520, 624, 652^e, 653	11	3889	1257	3889delAG	c.3770_3771del	p.(Glu1257Glyfs*9)	FS	BIC (23)^d
N4^e, 687, 724, 743	11	4184	1355	4184delTCAA	c.4065_4068del	p.(Asn1355Lysfs*10)	FS	BIC (144)^d
318^e	12	4302	1395	Q1395X	c.4183C>T	p.(Gln1395*)	NS	BIC (28)^d
408^e	13	4446	1443	R1443X	c.4327C>T	p.(Arg1443*)	NS	BIC (128)
523^e, 555, N18, 598^e, 612, 621	Intron 14	IVS14-1	-	IVS14-1G>A	c.4485-1G>A	Splice site	SP	BIC (2)^d
220^e, 275^e, 512^e	15	4627	1503	S1503X	c.4508C>A	p.(Ser1503*)	NS	BIC (1)^d
609^e	15	4784	1558	4784delG	c.4665del	p.(Arg1555Serfs*4)	FS	No
611^e	16	4981	1621	4981delA	c.4862del	p.(Asp1621Valfs*12)	FS	No
249^e, 658	17	5154	1679	5154delC	c.5035del	p.(Leu1679*)	FS	BIC (2)
276^e, 679	Intron 17	IVS17+1	-	IVS17+1G>A	c.5074+1G>A	Splice site	SP	BIC (3)
685	20	5358	1747	5358delC	c.5239del	p.(Gln1747Lysfs*18)	FS	LOVD (2)
734	20	5385	1756	5385dupC	c.5266dup	p.(Gln1756Profs*74)	FS	LOVD (376)
706	Intron 20	IVS20-1	-	IVS20-1G>C	c.5278-1G>C	Splice site	SP	LOVD (5)^d
678	21	5429	1771	5429dupG	c.5310dup	p.(Pro1771Alafs*59)	FS	LOVD (1)
278, 338^e	22	5480	1787	5480delTG	c.5361_5362del	p.(Cys1787Trpfs*42)	FS	ClinVar (3)
682	22	5496	1793	K1793X	c.5377A>T	p.(Lys1793*)	NS	ClinVar (1)
248^e	Intron 23	IVS23-2	-	IVS23-2A>T	c.5468-2A>T	Splice site	SP	ClinVar (1)
260, 264, 329^e, 377^e, 389, 439, 481, 501, 522	24	5622	1835	R1835X	c.5503C>T	p.(Arg1835*)	NS	BIC (74)^d
BRCA1-large genomic rearrangements^e
229, 291, 314, 379, 406, 498, 549	1-2	-	-	del exon 1-2	g.41271967_41308900del^f		LGR	(42)^g
261, 719	21-24	-	-	del exon 21-24	g.41172653_41205744del^f		LGR	No
BRCA2-small-range mutations
497, 700	3	320	31	W31X	c.92G>A	p.(Trp31*)	NS	ClinVar (4)
N26	Intron 4	IVS4-2	-	IVS4-2A>G	c.426-2A>G	Splice site	SP	ClinVar (4)
545	9	993	255	993delCACAA	c.765_769del	p.(Asn255Lysfs*19)	FS	No
330	10	1528	434	1528delAAAA	c.1300_1303del	p.(Lys434Glufs*25)	FS	ClinVar (2)
602	11	3048	941	3048delA	c.2820del	p.(Val941Cysfs*19)	FS	No
206	11	3063	945	3063delA	c.2835del	p.(Asp946Ilefs*14)	FS	ClinVar (2)
505	11	4088	1287	4088delA	c.3860del	p.(Asn1287Ilefs*6)	FS	BIC (2)
222, 407^h, 525, 540^h	11	5450	1741	5450delGTAA	c.5222_5225del	p.(Ser1741Thrfs*35)	FS	BIC (1)
627, 684	11	5910	1894	Y1894X	c.5682C>A	p.(Tyr1894*)	NS	BIC (3)
295^e	11	5950	1908	5950delCT	c.5722_5723del	p.(Leu1908Argfs*2)	FS	BIC (43)^d
447	11	6696	2156	6696delTC	c.6468_6469del	p.(Gln2157Ilefs*18)	FS	BIC (24)^d
548^h	11	7044	2274	7044delAAGAG	c.6816_6820del	p.(Gly2274Alafs*17)	FS	ClinVar (6)
579	15	7803	2526	7803delA	c.7575del	p.(Ala2526Glnfs*2)	FS	LOVD (2)
492	Intron 17	IVS17+2	-	IVS17+2C>A	c.7976+2C>A	Splice site	SP	ClinVar (1)
713	20	8773	2849	8773delAA	c.8545_8546del	p.(Lys2849Glyfs*19)	FS	No
702	20	8779	2860	8779_8798dup20	c.8551_8570dup	p.(Lys2860Asnfs*10)	FS	No
207^h	21	8897	2890	8897insT	c.8669dup	p.(Thr2891Asnfs*16)	FS	ClinVar (1)
538	Intron 21	IVS21+4	-	IVS21+4A>G	c.8754+4A>G	Splice site	SP	BIC (7)

^aNumbering starts at the first A of the first coding ATG (located in exon 2) of NCBI GenBank accession number U14680 (BRCA1) and U43746 (BRCA2)
^bFS frameshift mutation, LGR large genomic rearrangement, MS missense mutation, NS nonsense mutation, SP splice-site mutation
^cBIC Breast Cancer Information Core database (https://research.nhgri.nih.gov/projects/bic/), LOVD Leiden Open Variation Database (http://databases.lovd.nl/shared/genes/BRCA2); ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/), date last accessed June 26, 2018
^dPreviously reported in Pakistani breast/ovarian cancer cases [9, 10]
^eFamilies and mutation description have been previously reported [11, 18]
^fGenomic locale for chromosome 17, from the UCSC genome browser, Feb 2009 assembly
^gNot available in databases; reported in various studies [1, 11]
^hFamilies with male breast cancer

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