Variant 10-14934415-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001033855.3(DCLRE1C):c.643C>T(p.Leu215Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.394 in 1,613,398 control chromosomes in the GnomAD database, including 131,213 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 16737 hom., cov: 30)

Exomes 𝑓: 0.39 ( 114476 hom. )

Consequence

DCLRE1C
NM_001033855.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11O:1

Conservation

PhyloP100: 3.65

Variant links:

Genes affected

DCLRE1C (HGNC:17642): (DNA cross-link repair 1C) This gene encodes a nuclear protein that is involved in V(D)J recombination and DNA repair. The encoded protein has single-strand-specific 5'-3' exonuclease activity; it also exhibits endonuclease activity on 5' and 3' overhangs and hairpins. The protein also functions in the regulation of the cell cycle in response to DNA damage. Mutations in this gene can cause Athabascan-type severe combined immunodeficiency (SCIDA) and Omenn syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

DCLRE1C links:

DCLRE1C (HGNC:):

DCLRE1C links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 10-14934415-G-A is Benign according to our data. Variant chr10-14934415-G-A is described in ClinVar as [Benign]. Clinvar id is 36000.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCLRE1C	NM_001033855.3 linkuse as main transcript	c.643C>T	p.Leu215Leu	synonymous_variant	8/14	ENST00000378278.7	NP_001029027.1	Q96SD1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCLRE1C	ENST00000378278.7 linkuse as main transcript	c.643C>T	p.Leu215Leu	synonymous_variant	8/14	1	NM_001033855.3	ENSP00000367527.2		Q96SD1-1

Frequencies

GnomAD3 genomes

AF:

0.451

AC:

68424

AN:

151738

Hom.:

16692

Cov.:

show subpopulations

Gnomad AFR

AF:

0.646

Gnomad AMI

AF:

0.445

Gnomad AMR

AF:

0.441

Gnomad ASJ

AF:

0.432

Gnomad EAS

AF:

0.417

Gnomad SAS

AF:

0.544

Gnomad FIN

AF:

0.265

Gnomad MID

AF:

0.497

Gnomad NFE

AF:

0.360

Gnomad OTH

AF:

0.446

GnomAD3 exomes

AF:

0.416

AC:

104558

AN:

251182

Hom.:

23292

AF XY:

0.416

AC XY:

56524

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.655

Gnomad AMR exome

AF:

0.477

Gnomad ASJ exome

AF:

0.428

Gnomad EAS exome

AF:

0.409

Gnomad SAS exome

AF:

0.554

Gnomad FIN exome

AF:

0.262

Gnomad NFE exome

AF:

0.358

Gnomad OTH exome

AF:

0.392

GnomAD4 exome

AF:

0.388

AC:

567459

AN:

1461544

Hom.:

114476

Cov.:

AF XY:

0.393

AC XY:

285397

AN XY:

727062

show subpopulations

Gnomad4 AFR exome

AF:

0.663

Gnomad4 AMR exome

AF:

0.472

Gnomad4 ASJ exome

AF:

0.436

Gnomad4 EAS exome

AF:

0.471

Gnomad4 SAS exome

AF:

0.550

Gnomad4 FIN exome

AF:

0.262

Gnomad4 NFE exome

AF:

0.365

Gnomad4 OTH exome

AF:

0.405

GnomAD4 genome

AF:

0.451

AC:

68536

AN:

151854

Hom.:

16737

Cov.:

AF XY:

0.450

AC XY:

33393

AN XY:

74214

show subpopulations

Gnomad4 AFR

AF:

0.647

Gnomad4 AMR

AF:

0.442

Gnomad4 ASJ

AF:

0.432

Gnomad4 EAS

AF:

0.419

Gnomad4 SAS

AF:

0.543

Gnomad4 FIN

AF:

0.265

Gnomad4 NFE

AF:

0.360

Gnomad4 OTH

AF:

0.444

Alfa

AF:

0.384

Hom.:

4954

Bravo

AF:

0.472

Asia WGS

AF:

0.454

AC:

1579

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 65% of patients studied by a panel of primary immunodeficiencies. Number of patients: 57. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Histiocytic medullary reticulosis

Benign:3

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -

not provided

Benign:2Other:1

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Severe combined immunodeficiency due to DCLRE1C deficiency

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Severe combined immunodeficiency disease

Benign:1

Benign, criteria provided, single submitter

clinical testing;curation

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Aug 18, 2011

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

5.6

DANN

Benign

0.78

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