Prevalence of RECQL germline variants in Pakistani early-onset and familial breast cancer patients

Rashid, Muhammad Usman; Muhammad, Noor; Khan, Faiz Ali; Shehzad, Umara; Naeemi, Humaira; Malkani, Naila; Hamann, Ute

doi:10.1186/s13053-020-00159-6

Hereditary Cancer in Clinical Practice

Table 2 RECQL germline variants identified in the study cases and controls from Pakistan

From: Prevalence of RECQL germline variants in Pakistani early-onset and familial breast cancer patients

Location	Coding (c.) DNA Sequence^a	Effect	Prevalence n (%)		MAF (%)			Classification	Reference
Location	Coding (c.) DNA Sequence^a	Effect	Cases (n = 302)	Controls (n = 250)	Cases	Controls	gnomAD, SAS	Classification	Reference
Pathogenic variant
Exon 4	c.225G > A (p.W75*)	Nonsense	1 (0.3)	0 (0.0)	0.166	0	NA	P^b	Novel
Variants of uncertain significance
Exon 5	c.421A > T (p.I141F)	Missense	1 (0.3)	0 (0.0)	0.166	0	0.0188	VUS^b	Novel
Exon 6	c.546C > T (p.S182S)	Silent	1 (0.3)	0 (0.0)	0.166	0	0.0165	VUS^b	Novel
Exon 12	c.1425C > T (p.C475C)	Silent	1 (0.3)	0 (0.0)	0.166	0	0.0033	VUS^b	Novel
Benign variants
Coding
Exon 3	c.132G > A (p.K44K)	Silent	34 (11.3)	28 (11.2)	5.629	5.6	NA	B	Novel
Exon 3	c.151G > A (p.E51K)	Missense	49 (16.2)	34 (13.6)	8.113	6.8	0.0098	B	Novel
Exon 7	c.833C > G (p.T278R)	Missense	5 (1.7)	6 (2.4)	0.828	1.2	1.6417	B	ClinVar, [10]
Exon 8	c.898 T > A (p.F300I)	Missense	1 (0.3)	0 (0.0)	0.166	0	0.0033	B	[6, 10]
Exon 13	c.1651A > G (p.I551V)	Missense	1 (0.3)	1 (0.4)	0.166	0.2	0.0785	LB^b	Novel
Exon 13	c.1661A > G (p.Y554C)	Missense	5 (1.7)	1 (0.4)	0.828	0.2	0.2366	LB	[10]
Non-coding variants
5’UTR	c.-110G > A	5’UTR	2 (0.7)	3 (1.2)	0.331	0.6	NA	B	Novel
5’UTR	c.-137C > T	5’UTR	3 (1.0)	3 (1.2)	0.497	0.6	NA	B	ClinVar, [22]
5’UTR	c.-187 T > G	5’UTR	1 (0.3)	0 (0.0)	0.166	0	NA	B	Novel
Intron 3	c.215-169C > A	Intronic	22 (7.3)	20 (8.0)	3.642	4.0	0	LB	ClinVar
Intron 3	c.215-86G > A	Intronic	1 (0.3)	1 (0.4)	0.166	0.2	0	B	[22]
Intron 3	c.215-48C > A	Intronic	1 (0.3)	1 (0.4)	0.166	0.2	0.0663	B	Novel
Intron 3	c.215-37 T > C	Intronic	1 (0.3)	0 (0.0)	0.166	0	0.0174	B	Novel
Intron 6	c.700 + 110C > G	Intronic	1 (0.3)	0 (0.0)	0.166	0	NA	B	Novel
Intron 7	c.868-11G > A	Intronic	1 (0.3)	1 (0.4)	0.166	0.2	0.0611	B	Novel
Intron 7	c.868-2A > G	Intronic	3 (1.0)	2 (0.8)	0.497	0.4	0.5669	B^b	Novel
Intron 8	c.949 + 62A > G	Intronic	1 (0.3)	0 (0.0)	0.166	0	NA	B	Novel
Intron 8	c.949 + 76A > G	Intronic	6 (2.0)	6 (2.4)	0.993	1.2	0	LB	ClinVar
Intron 11	c.1355 + 30 T > C	Intronic	13 (4.3)	17 (6.8)	2.152	3.4	51.4	B	[22]
Intron 11	c.1355 + 103G > C	Intronic	5 (1.7)	11 (4.4)	0.828	2.2	0	B	ClinVar, [22]
Intron 12	c.1448-18A > G	Intronic	1 (0.3)	0 (0.0)	0.166	0	0	B	Novel
Intron 13	c.1667 + 53 T > A	Intronic	2 (0.7)	1 (0.4)	0.331	0.2	0	B	ClinVar
Intron 13	c.1667 + 53delT	Intronic	1 (0.3)	0 (0.0)	0.166	0	0	B	Novel
Intron 13	c.1668-160C > T	Intronic	1 (0.3)	0 (0.0)	0.166	0	0	B	Novel
Intron 13	c.1668-81G > A	Intronic	3 (1.0)	4 (1.6)	0.497	0.8	0	B	Novel
Intron 14	c.1797 + 14_17delAATT	Intronic	20 (6.6)	22 (8.8)	3.311	4.4	4.0024	B	Novel
3’UTR	c.*6A > C	3’UTR	61 (20.2)	84 (33.6)	10.099	16.8	NA	B	[22]

B Benign, gnomAD Genome aggregation database, LB Likely benign, LP Likely pathogenic, MAF Minor allele frequency, NA Not available, P Pathogenic, SAS South Asians, VUS Variant of uncertain significance
^aNomenclature follows Human Genome Variation Society (HGVS) (http://www.hgvs.org). Numbering start at the first A of the first coding ATG (located in exon 2) of NCBI GenBank Accession NM_002907.3
^bClassification of nucleotide alterations was performed using Sherloc guidelines [21]

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