rs2159943

chr12-21474811-A-Gchr12-21474811-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002907.4(RECQL):c.1355+30T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 1,598,170 control chromosomes in the GnomAD database, including 155,392 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.35 (11036 hom., cov: 33)
  • Exomes 𝑓: 0.44 (144356 hom.)
• Consequence: RECQL NM_002907.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.116

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 12-21474811-A-G is Benign according to our data. Variant chr12-21474811-A-G is described in ClinVar as [Benign]. Clinvar id is 679689.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RECQL	NM_002907.4	c.1355+30T>C		intron_variant		ENST00000444129.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RECQL	ENST00000444129.7	c.1355+30T>C		intron_variant		2	NM_002907.4	P1
RECQL	ENST00000421138.6	c.1355+30T>C		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53775 AN: 151844 Hom.: 11039 Cov.: 33

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.347

GnomAD3 exomes AF: 0.435 AC: 107742 AN: 247490 Hom.: 24530 AF XY: 0.442 AC XY: 59232 AN XY: 133916

Gnomad AFR exome AF: 0.120

Gnomad AMR exome AF: 0.483

Gnomad ASJ exome AF: 0.457

Gnomad EAS exome AF: 0.432

Gnomad SAS exome AF: 0.514

Gnomad FIN exome AF: 0.459

Gnomad NFE exome AF: 0.440

Gnomad OTH exome AF: 0.432

GnomAD4 exome AF: 0.442 AC: 639569 AN: 1446210 Hom.: 144356 Cov.: 27 AF XY: 0.445 AC XY: 320331 AN XY: 720002

Gnomad4 AFR exome AF: 0.109

Gnomad4 AMR exome AF: 0.471

Gnomad4 ASJ exome AF: 0.459

Gnomad4 EAS exome AF: 0.434

Gnomad4 SAS exome AF: 0.513

Gnomad4 FIN exome AF: 0.461

Gnomad4 NFE exome AF: 0.447

Gnomad4 OTH exome AF: 0.415

GnomAD4 genome AF: 0.354 AC: 53771 AN: 151960 Hom.: 11036 Cov.: 33 AF XY: 0.360 AC XY: 26721 AN XY: 74272

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.466

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.516

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.342

Alfa AF: 0.399 Hom.: 2925

Bravo AF: 0.338

Asia WGS AF: 0.404 AC: 1403 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 18, 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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	2.2
Dann	Benign	0.68

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: rs2159943; hg19: chr12-21627745; COSMIC: COSV53709921; COSMIC: COSV53709921;