NM_002907.4:c.1216+82G>A

Variant names:

• chr12-21475386-C-T
• rs10841831
• NM_002907.4:c.1216+82G>A

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.1216+82G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 848,098 control chromosomes in the GnomAD database, including 99,214 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (18150 hom., cov: 32)
  • Exomes 𝑓: 0.48 (81064 hom.)
• Consequence: RECQL NM_002907.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.23
• Publications: 7 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=-0.82).
• BP6: Variant 12-21475386-C-T is Benign according to our data. Variant chr12-21475386-C-T is described in ClinVar as Benign. ClinVar VariationId is 679688.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL	NM_002907.4	c.1216+82G>A		intron_variant	Intron 10 of 14	ENST00000444129.7	NP_002898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RECQL	ENST00000444129.7	c.1216+82G>A		intron_variant	Intron 10 of 14	2	NM_002907.4	ENSP00000416739.2
RECQL	ENST00000421138.6	c.1216+82G>A		intron_variant	Intron 11 of 15	1		ENSP00000395449.2

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74034 AN: 151194 Hom.: 18122 Cov.: 32

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.491

GnomAD4 exome AF: 0.481 AC: 335120 AN: 696784 Hom.: 81064 AF XY: 0.478 AC XY: 174872 AN XY: 365898

African (AFR) AF: 0.502 AC: 8616 AN: 17178

American (AMR) AF: 0.463 AC: 12807 AN: 27634

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 7133 AN: 16746

East Asian (EAS) AF: 0.560 AC: 19752 AN: 35258

South Asian (SAS) AF: 0.431 AC: 23389 AN: 54244

European-Finnish (FIN) AF: 0.498 AC: 22792 AN: 45792

Middle Eastern (MID) AF: 0.532 AC: 2170 AN: 4076

European-Non Finnish (NFE) AF: 0.480 AC: 221743 AN: 461532

Other (OTH) AF: 0.487 AC: 16718 AN: 34324

GnomAD4 genome AF: 0.490 AC: 74106 AN: 151314 Hom.: 18150 Cov.: 32 AF XY: 0.489 AC XY: 36162 AN XY: 73894

African (AFR) AF: 0.504 AC: 20782 AN: 41224

American (AMR) AF: 0.491 AC: 7475 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1447 AN: 3468

East Asian (EAS) AF: 0.541 AC: 2775 AN: 5134

South Asian (SAS) AF: 0.437 AC: 2107 AN: 4818

European-Finnish (FIN) AF: 0.496 AC: 5205 AN: 10486

Middle Eastern (MID) AF: 0.527 AC: 154 AN: 292

European-Non Finnish (NFE) AF: 0.482 AC: 32633 AN: 67654

Other (OTH) AF: 0.497 AC: 1048 AN: 2110

Alfa AF: 0.486 Hom.: 2338

Bravo AF: 0.492

Asia WGS AF: 0.542 AC: 1884 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 20, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.82
CADD	Benign	6.5
DANN	Benign	0.27
PhyloP100		1.2
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: rs10841831; hg19: chr12-21628320;