NM_002907.4:c.868-68dupG

Variant names:

• chr12-21477059-A-AC
• rs5796903
• NM_002907.4:c.868-68dupG

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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
• hereditary breast carcinoma

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• familial ovarian cancer

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002907.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL	NM_002907.4	MANE Select	c.868-68dupG		intron	N/A	NP_002898.2
	RECQL	NM_032941.3		c.868-68dupG		intron	N/A	NP_116559.1	P46063

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL	ENST00000444129.7	TSL:2 MANE Select	c.868-68_868-67insG		intron	N/A	ENSP00000416739.2	P46063
	RECQL	ENST00000421138.6	TSL:1	c.868-68_868-67insG		intron	N/A	ENSP00000395449.2	P46063
	RECQL	ENST00000965023.1		c.898-68_898-67insG		intron	N/A	ENSP00000635082.1

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

African (AFR) AF: 0.520 AC: 10395 AN: 20002

American (AMR) AF: 0.491 AC: 12124 AN: 24712

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 8508 AN: 19556

East Asian (EAS) AF: 0.569 AC: 19034 AN: 33458

South Asian (SAS) AF: 0.445 AC: 25963 AN: 58332

European-Finnish (FIN) AF: 0.507 AC: 21347 AN: 42126

Middle Eastern (MID) AF: 0.529 AC: 2403 AN: 4546

European-Non Finnish (NFE) AF: 0.492 AC: 313669 AN: 637750

Other (OTH) AF: 0.497 AC: 20116 AN: 40462

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

African (AFR) AF: 0.509 AC: 21104 AN: 41428

American (AMR) AF: 0.494 AC: 7540 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1455 AN: 3468

East Asian (EAS) AF: 0.545 AC: 2816 AN: 5166

South Asian (SAS) AF: 0.438 AC: 2114 AN: 4826

European-Finnish (FIN) AF: 0.501 AC: 5299 AN: 10580

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.489 AC: 33173 AN: 67880

Other (OTH) AF: 0.498 AC: 1048 AN: 2104

Alfa AF: 0.488 Hom.: 2207

Asia WGS AF: 0.546 AC: 1903 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.63
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: rs5796903; hg19: chr12-21629993;