chr12-21477059-A-AC

Position:

• chr12-21477059-A-AC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002907.4(RECQL):​c.868-68dupG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 1,032,868 control chromosomes in the GnomAD database, including 129,333 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.50 (18698 hom., cov: 0)
  • Exomes 𝑓: 0.49 (110635 hom.)
• Consequence: RECQL NM_002907.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.629

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 12-21477059-A-AC is Benign according to our data. Variant chr12-21477059-A-AC is described in ClinVar as [Benign]. Clinvar id is 679682.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RECQL	NM_002907.4	c.868-68dupG		intron_variant		ENST00000444129.7	NP_002898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RECQL	ENST00000444129.7	c.868-68dupG		intron_variant		2	NM_002907.4	ENSP00000416739.2
RECQL	ENST00000421138.6	c.868-68dupG		intron_variant		1		ENSP00000395449.2

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75142 AN: 151804 Hom.: 18671 Cov.: 0

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.545

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.492

GnomAD4 exome AF: 0.492 AC: 433559 AN: 880944 Hom.: 110635 AF XY: 0.490 AC XY: 221750 AN XY: 452608

Gnomad4 AFR exome AF: 0.520

Gnomad4 AMR exome AF: 0.491

Gnomad4 ASJ exome AF: 0.435

Gnomad4 EAS exome AF: 0.569

Gnomad4 SAS exome AF: 0.445

Gnomad4 FIN exome AF: 0.507

Gnomad4 NFE exome AF: 0.492

Gnomad4 OTH exome AF: 0.497

GnomAD4 genome AF: 0.495 AC: 75212 AN: 151924 Hom.: 18698 Cov.: 0 AF XY: 0.495 AC XY: 36731 AN XY: 74268

Gnomad4 AFR AF: 0.509

Gnomad4 AMR AF: 0.494

Gnomad4 ASJ AF: 0.420

Gnomad4 EAS AF: 0.545

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.501

Gnomad4 NFE AF: 0.489

Gnomad4 OTH AF: 0.498

Alfa AF: 0.488 Hom.: 2207

Asia WGS AF: 0.546 AC: 1903 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2018

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs5796903; hg19: chr12-21629993;