Variant 10-113841516-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_014881.5(DCLRE1A):c.2710A>C(p.Lys904Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000942 in 1,612,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000099 ( 0 hom. )

Consequence

DCLRE1A
NM_014881.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.22

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.854

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCLRE1A	NM_014881.5 linkuse as main transcript	c.2710A>C	p.Lys904Gln	missense_variant	7/9	ENST00000361384.7	NP_055696.3	Q6PJP8
DCLRE1A	NM_001271816.2 linkuse as main transcript	c.2710A>C	p.Lys904Gln	missense_variant	8/10		NP_001258745.1	Q6PJP8
DCLRE1A	XM_006718090.2 linkuse as main transcript	c.2710A>C	p.Lys904Gln	missense_variant	8/10		XP_006718153.1	Q6PJP8
DCLRE1A	XM_011540429.2 linkuse as main transcript	c.2710A>C	p.Lys904Gln	missense_variant	8/10		XP_011538731.1	Q6PJP8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCLRE1A	ENST00000361384.7 linkuse as main transcript	c.2710A>C	p.Lys904Gln	missense_variant	7/9	1	NM_014881.5	ENSP00000355185.2		Q6PJP8
DCLRE1A	ENST00000369305.1 linkuse as main transcript	c.2710A>C	p.Lys904Gln	missense_variant	8/10	5		ENSP00000358311.1		Q6PJP8

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000520

AC:

AN:

250092

Hom.:

AF XY:

0.0000592

AC XY:

AN XY:

135234

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000993

AC:

145

AN:

1460606

Hom.:

Cov.:

AF XY:

0.0000853

AC XY:

AN XY:

726590

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:

0.000126

Gnomad4 OTH exome

AF:

0.0000829

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000901

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000238

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 05, 2024

The c.2710A>C (p.K904Q) alteration is located in exon 7 (coding exon 7) of the DCLRE1A gene. This alteration results from a A to C substitution at nucleotide position 2710, causing the lysine (K) at amino acid position 904 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.77

BayesDel_addAF

Benign

-0.026

BayesDel_noAF

Uncertain

-0.060

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.44

T;T

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.84

.;T

M_CAP

Uncertain

0.090

MetaRNN

Pathogenic

0.85

D;D

MetaSVM

Uncertain

0.33

MutationAssessor

Pathogenic

3.5

M;M

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-3.1

D;D

REVEL

Uncertain

0.59

Sift

Uncertain

0.0080

D;D

Sift4G

Uncertain

0.010

D;D

Polyphen

0.88

P;P

Vest4

0.85

MVP

0.91

MPC

0.36

ClinPred

0.86

GERP RS

5.1

Varity_R

0.74

gMVP

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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