Variant 1-50418864-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_032110.3(DMRTA2):c.1430G>A(p.Ser477Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00935 in 1,538,058 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S477R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0066 ( 5 hom., cov: 34)

Exomes 𝑓: 0.0097 ( 83 hom. )

Consequence

DMRTA2
NM_032110.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.35

Variant links:

Genes affected

DMRTA2 (HGNC:13908): (DMRT like family A2) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II and sex differentiation. Predicted to act upstream of or within nervous system development and skeletal muscle cell differentiation. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

DMRTA2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008152574).

BP6

Variant 1-50418864-C-T is Benign according to our data. Variant chr1-50418864-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1337061.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMRTA2	NM_032110.3 linkuse as main transcript	c.1430G>A	p.Ser477Asn	missense_variant	3/3	ENST00000404795.4	NP_115486.1	Q96SC8
DMRTA2	XM_011541937.3 linkuse as main transcript	c.1430G>A	p.Ser477Asn	missense_variant	2/2		XP_011540239.1	Q96SC8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMRTA2	ENST00000404795.4 linkuse as main transcript	c.1430G>A	p.Ser477Asn	missense_variant	3/3	5	NM_032110.3	ENSP00000383909.3		Q96SC8
DMRTA2	ENST00000418121.5 linkuse as main transcript	c.1430G>A	p.Ser477Asn	missense_variant	2/2	1		ENSP00000399370.1		Q96SC8

Frequencies

GnomAD3 genomes

AF:

0.00662

AC:

1007

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00183

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00707

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00622

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0107

Gnomad OTH

AF:

0.00956

GnomAD3 exomes

AF:

0.00697

AC:

956

AN:

137100

Hom.:

AF XY:

0.00769

AC XY:

599

AN XY:

77906

show subpopulations

Gnomad AFR exome

AF:

0.00199

Gnomad AMR exome

AF:

0.00645

Gnomad ASJ exome

AF:

0.00259

Gnomad EAS exome

AF:

0.000130

Gnomad SAS exome

AF:

0.00410

Gnomad FIN exome

AF:

0.00509

Gnomad NFE exome

AF:

0.0102

Gnomad OTH exome

AF:

0.00915

GnomAD4 exome

AF:

0.00965

AC:

13373

AN:

1385766

Hom.:

Cov.:

AF XY:

0.00964

AC XY:

6622

AN XY:

687024

show subpopulations

Gnomad4 AFR exome

AF:

0.00160

Gnomad4 AMR exome

AF:

0.00645

Gnomad4 ASJ exome

AF:

0.00178

Gnomad4 EAS exome

AF:

0.0000605

Gnomad4 SAS exome

AF:

0.00344

Gnomad4 FIN exome

AF:

0.00564

Gnomad4 NFE exome

AF:

0.0111

Gnomad4 OTH exome

AF:

0.00933

GnomAD4 genome

AF:

0.00661

AC:

1007

AN:

152292

Hom.:

Cov.:

AF XY:

0.00631

AC XY:

470

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00183

Gnomad4 AMR

AF:

0.00706

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00622

Gnomad4 NFE

AF:

0.0107

Gnomad4 OTH

AF:

0.00993

Alfa

AF:

0.00910

Hom.:

Bravo

AF:

0.00676

TwinsUK

AF:

0.00890

AC:

ALSPAC

AF:

0.0119

AC:

ESP6500AA

AF:

0.00105

AC:

ESP6500EA

AF:

0.00816

AC:

ExAC

AF:

0.00516

AC:

580

Asia WGS

AF:

0.00173

AC:

AN:

3472

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Sep 17, 2018

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.57

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.023

T;T

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.083

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.60

.;T

MetaRNN

Benign

0.0082

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

N;N

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.76

N;N

REVEL

Benign

0.13

Sift

Benign

0.23

T;T

Sift4G

Benign

0.45

T;T

Polyphen

0.90

P;P

Vest4

0.43

MVP

0.061

ClinPred

0.018

GERP RS

4.2

Varity_R

0.26

gMVP

0.43

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