rs10841834

Variant names:

• chr12-21491733-G-A
• rs10841834
• NM_002907.4:c.17-17C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002907.4(RECQL):​c.17-17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 1,589,552 control chromosomes in the GnomAD database, including 167,624 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (12151 hom., cov: 31)
  • Exomes 𝑓: 0.46 (155473 hom.)
• Consequence: RECQL NM_002907.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.04
• Publications: 9 publications found

Genes affected

RECQL (HGNC:9948): (RecQ like helicase) The protein encoded by this gene is a member of the RecQ DNA helicase family. DNA helicases are enzymes involved in various types of DNA repair, including mismatch repair, nucleotide excision repair and direct repair. The encoded protein is involved in the processing of Holliday junctions, the suppression of sister chromatid exchanges, telomere maintenance, and is required for genotoxic stress resistance. Defects in this gene have been associated with several types of cancer. [provided by RefSeq, Jan 2017]

RECQL Gene-Disease associations (from GenCC):

• RECON progeroid syndrome

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• breast cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics
• familial ovarian cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• hereditary breast carcinoma

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 12-21491733-G-A is Benign according to our data. Variant chr12-21491733-G-A is described in ClinVar as Benign. ClinVar VariationId is 679680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL	NM_002907.4	c.17-17C>T		intron_variant	Intron 2 of 14	ENST00000444129.7	NP_002898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RECQL	ENST00000444129.7	c.17-17C>T		intron_variant	Intron 2 of 14	2	NM_002907.4	ENSP00000416739.2

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57487 AN: 151814 Hom.: 12152 Cov.: 31

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.361

GnomAD2 exomes AF: 0.449 AC: 101327 AN: 225818 AF XY: 0.454

Gnomad AFR exome AF: 0.172

Gnomad AMR exome AF: 0.484

Gnomad ASJ exome AF: 0.460

Gnomad EAS exome AF: 0.448

Gnomad FIN exome AF: 0.487

Gnomad NFE exome AF: 0.460

Gnomad OTH exome AF: 0.441

GnomAD4 exome AF: 0.462 AC: 664131 AN: 1437620 Hom.: 155473 Cov.: 29 AF XY: 0.463 AC XY: 330952 AN XY: 714328

African (AFR) AF: 0.159 AC: 5128 AN: 32216

American (AMR) AF: 0.468 AC: 18755 AN: 40050

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 11674 AN: 25266

East Asian (EAS) AF: 0.449 AC: 17745 AN: 39542

South Asian (SAS) AF: 0.493 AC: 40546 AN: 82164

European-Finnish (FIN) AF: 0.488 AC: 25660 AN: 52634

Middle Eastern (MID) AF: 0.309 AC: 1743 AN: 5646

European-Non Finnish (NFE) AF: 0.470 AC: 517329 AN: 1100792

Other (OTH) AF: 0.431 AC: 25551 AN: 59310

GnomAD4 genome AF: 0.378 AC: 57501 AN: 151932 Hom.: 12151 Cov.: 31 AF XY: 0.382 AC XY: 28347 AN XY: 74256

African (AFR) AF: 0.173 AC: 7165 AN: 41432

American (AMR) AF: 0.407 AC: 6218 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1624 AN: 3472

East Asian (EAS) AF: 0.463 AC: 2388 AN: 5156

South Asian (SAS) AF: 0.496 AC: 2389 AN: 4816

European-Finnish (FIN) AF: 0.491 AC: 5173 AN: 10534

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.461 AC: 31341 AN: 67948

Other (OTH) AF: 0.357 AC: 749 AN: 2100

Alfa AF: 0.420 Hom.: 5590

Bravo AF: 0.362

Asia WGS AF: 0.407 AC: 1412 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 18, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.8
DANN	Benign	0.42
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10841834; hg19: chr12-21644667; COSMIC: COSV59084253;