rs2159943

Variant names:

• chr12-21474811-A-G
• rs2159943
• NM_002907.4:c.1355+30T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-21474811-A-G
• chr12-21474811-A-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.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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.116
• Publications: 8 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=-0.81).
• BP6: Variant 12-21474811-A-G is Benign according to our data. Variant chr12-21474811-A-G is described in ClinVar as Benign. ClinVar VariationId 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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL	NM_002907.4	MANE Select	c.1355+30T>C		intron	N/A	NP_002898.2
	RECQL	NM_032941.3		c.1355+30T>C		intron	N/A	NP_116559.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL	ENST00000444129.7	TSL:2 MANE Select	c.1355+30T>C		intron	N/A	ENSP00000416739.2
	RECQL	ENST00000421138.6	TSL:1	c.1355+30T>C		intron	N/A	ENSP00000395449.2

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

GnomAD2 exomes AF: 0.435 AC: 107742 AN: 247490 AF XY: 0.442

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 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

African (AFR) AF: 0.109 AC: 3600 AN: 33026

American (AMR) AF: 0.471 AC: 20687 AN: 43882

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 11838 AN: 25816

East Asian (EAS) AF: 0.434 AC: 17165 AN: 39550

South Asian (SAS) AF: 0.513 AC: 43845 AN: 85522

European-Finnish (FIN) AF: 0.461 AC: 24535 AN: 53202

Middle Eastern (MID) AF: 0.307 AC: 1751 AN: 5700

European-Non Finnish (NFE) AF: 0.447 AC: 491359 AN: 1099760

Other (OTH) AF: 0.415 AC: 24789 AN: 59752

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

African (AFR) AF: 0.127 AC: 5266 AN: 41532

American (AMR) AF: 0.413 AC: 6298 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 1615 AN: 3462

East Asian (EAS) AF: 0.451 AC: 2336 AN: 5176

South Asian (SAS) AF: 0.516 AC: 2488 AN: 4820

European-Finnish (FIN) AF: 0.465 AC: 4914 AN: 10570

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.438 AC: 29712 AN: 67826

Other (OTH) AF: 0.342 AC: 722 AN: 2112

Alfa AF: 0.399 Hom.: 2925

Bravo AF: 0.338

Asia WGS AF: 0.404 AC: 1403 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.2
DANN	Benign	0.68
PhyloP100		-0.12
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: rs2159943; hg19: chr12-21627745; COSMIC: COSV53709921; COSMIC: COSV53709921;