Variant rs2159943 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.116

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
RECQL	NM_002907.4 linkuse as main transcript	c.1355+30T>C		intron_variant		ENST00000444129.7	NP_002898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RECQL	ENST00000444129.7 linkuse as main transcript	c.1355+30T>C		intron_variant		2	NM_002907.4	ENSP00000416739.2		P46063
RECQL	ENST00000421138.6 linkuse as main transcript	c.1355+30T>C		intron_variant		1		ENSP00000395449.2		P46063

Frequencies

GnomAD3 genomes

AF:

0.354

AC:

53775

AN:

151844

Hom.:

11039

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.445

AC XY:

320331

AN XY:

720002

show subpopulations

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.:

AF XY:

0.360

AC XY:

26721

AN XY:

74272

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over