Variant 10-113844168-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014881.5(DCLRE1A):c.2455G>T(p.Asp819Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 1,614,054 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

DCLRE1A
NM_014881.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.37

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCLRE1A	NM_014881.5 linkuse as main transcript	c.2455G>T	p.Asp819Tyr	missense_variant	5/9	ENST00000361384.7	NP_055696.3	Q6PJP8
DCLRE1A	NM_001271816.2 linkuse as main transcript	c.2455G>T	p.Asp819Tyr	missense_variant	6/10		NP_001258745.1	Q6PJP8
DCLRE1A	XM_006718090.2 linkuse as main transcript	c.2455G>T	p.Asp819Tyr	missense_variant	6/10		XP_006718153.1	Q6PJP8
DCLRE1A	XM_011540429.2 linkuse as main transcript	c.2455G>T	p.Asp819Tyr	missense_variant	6/10		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.2455G>T	p.Asp819Tyr	missense_variant	5/9	1	NM_014881.5	ENSP00000355185.2		Q6PJP8
DCLRE1A	ENST00000369305.1 linkuse as main transcript	c.2455G>T	p.Asp819Tyr	missense_variant	6/10	5		ENSP00000358311.1		Q6PJP8

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251462

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135902

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:

0.0000528

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000349

AC:

AN:

1461874

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

727236

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:

0.0000423

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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 03, 2023

The c.2455G>T (p.D819Y) alteration is located in exon 5 (coding exon 5) of the DCLRE1A gene. This alteration results from a G to T substitution at nucleotide position 2455, causing the aspartic acid (D) at amino acid position 819 to be replaced by a tyrosine (Y). 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

Benign

0.24

BayesDel_addAF

Uncertain

0.078

BayesDel_noAF

Uncertain

0.0

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.52

D;D

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.27

FATHMM_MKL

Uncertain

0.86

LIST_S2

Pathogenic

0.98

.;D

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.74

D;D

MetaSVM

Benign

-0.42

MutationAssessor

Pathogenic

3.3

M;M

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-5.2

D;D

REVEL

Uncertain

0.48

Sift

Uncertain

0.019

D;D

Sift4G

Uncertain

0.0080

D;D

Polyphen

0.25

B;B

Vest4

0.80

MutPred

0.42

Loss of disorder (P = 0.0115);Loss of disorder (P = 0.0115);

MVP

0.83

MPC

0.56

ClinPred

0.88

GERP RS

2.6

Varity_R

0.71

gMVP

0.94

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