Variant chr10-113849181-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_014881.5(DCLRE1A):c.1924A>G(p.Asn642Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

DCLRE1A
NM_014881.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.630

Variant links:

Genes affected

DCLRE1A (HGNC:17660): (DNA cross-link repair 1A) This gene encodes a conserved protein that is involved in the repair of DNA interstrand cross-links. DNA cross-links suppress transcription, replication, and DNA segregation. The encoded protein is a regulator of the mitotic cell cycle checkpoint. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

DCLRE1A links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.019527793).

BP6

Variant 10-113849181-T-C is Benign according to our data. Variant chr10-113849181-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2614515.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DCLRE1A	NM_014881.5 linkuse as main transcript	c.1924A>G	p.Asn642Asp	missense_variant	2/9	ENST00000361384.7	NP_055696.3
DCLRE1A	NM_001271816.2 linkuse as main transcript	c.1924A>G	p.Asn642Asp	missense_variant	3/10		NP_001258745.1
DCLRE1A	XM_006718090.2 linkuse as main transcript	c.1924A>G	p.Asn642Asp	missense_variant	3/10		XP_006718153.1
DCLRE1A	XM_011540429.2 linkuse as main transcript	c.1924A>G	p.Asn642Asp	missense_variant	3/10		XP_011538731.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
DCLRE1A	ENST00000361384.7 linkuse as main transcript	c.1924A>G	p.Asn642Asp	missense_variant	2/9	1	NM_014881.5	ENSP00000355185	P1
	ENST00000692647.1 linkuse as main transcript	n.139-3444T>C		intron_variant, non_coding_transcript_variant
DCLRE1A	ENST00000369305.1 linkuse as main transcript	c.1924A>G	p.Asn642Asp	missense_variant	3/10	5		ENSP00000358311	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461722

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727154

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 26, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

4.9

DANN

Benign

0.44

DEOGEN2

Benign

0.039

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.54

.;T

M_CAP

Benign

0.0062

MetaRNN

Benign

0.020

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.22

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

0.23

N;N

REVEL

Benign

0.055

Sift

Benign

0.80

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.031

MutPred

0.23

Loss of MoRF binding (P = 0.0628);Loss of MoRF binding (P = 0.0628);

MVP

0.45

MPC

0.13

ClinPred

0.026

GERP RS

0.71

Varity_R

0.030

gMVP

0.080

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