Variant chr1-50419077-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_032110.3(DMRTA2):c.1217T>A(p.Leu406Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00343 in 1,260,936 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.0026 ( 2 hom., cov: 34)

Exomes 𝑓: 0.0035 ( 19 hom. )

Consequence

DMRTA2
NM_032110.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 1.17

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006879717).

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMRTA2	NM_032110.3 linkuse as main transcript	c.1217T>A	p.Leu406Gln	missense_variant	3/3	ENST00000404795.4	NP_115486.1	Q96SC8
DMRTA2	XM_011541937.3 linkuse as main transcript	c.1217T>A	p.Leu406Gln	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.1217T>A	p.Leu406Gln	missense_variant	3/3	5	NM_032110.3	ENSP00000383909.3		Q96SC8
DMRTA2	ENST00000418121.5 linkuse as main transcript	c.1217T>A	p.Leu406Gln	missense_variant	2/2	1		ENSP00000399370.1		Q96SC8

Frequencies

GnomAD3 genomes

AF:

0.00264

AC:

394

AN:

149502

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000778

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00353

Gnomad ASJ

AF:

0.00174

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.000418

Gnomad MID

AF:

0.0161

Gnomad NFE

AF:

0.00402

Gnomad OTH

AF:

0.00583

GnomAD3 exomes

AF:

0.00168

AC:

AN:

8328

Hom.:

AF XY:

0.00178

AC XY:

AN XY:

5060

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00277

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00130

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00202

Gnomad OTH exome

AF:

0.00376

GnomAD4 exome

AF:

0.00354

AC:

3939

AN:

1111324

Hom.:

Cov.:

AF XY:

0.00356

AC XY:

1913

AN XY:

536674

show subpopulations

Gnomad4 AFR exome

AF:

0.000406

Gnomad4 AMR exome

AF:

0.00509

Gnomad4 ASJ exome

AF:

0.00219

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00316

Gnomad4 FIN exome

AF:

0.000301

Gnomad4 NFE exome

AF:

0.00375

Gnomad4 OTH exome

AF:

0.00425

GnomAD4 genome

AF:

0.00262

AC:

392

AN:

149612

Hom.:

Cov.:

AF XY:

0.00259

AC XY:

189

AN XY:

73000

show subpopulations

Gnomad4 AFR

AF:

0.000776

Gnomad4 AMR

AF:

0.00346

Gnomad4 ASJ

AF:

0.00174

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.000418

Gnomad4 NFE

AF:

0.00402

Gnomad4 OTH

AF:

0.00576

Alfa

AF:

0.00324

Hom.:

Bravo

AF:

0.00290

ExAC

AF:

0.00104

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Jul 09, 2019	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Ambry Genetics	Nov 14, 2023	The c.1217T>A (p.L406Q) alteration is located in exon 3 (coding exon 2) of the DMRTA2 gene. This alteration results from a T to A substitution at nucleotide position 1217, causing the leucine (L) at amino acid position 406 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.014

T;T

Eigen

Benign

-0.092

Eigen_PC

Benign

-0.095

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.56

.;T

MetaRNN

Benign

0.0069

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;L

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

0.47

N;N

REVEL

Benign

0.098

Sift

Benign

0.21

T;T

Sift4G

Benign

0.57

T;T

Polyphen

0.97

D;D

Vest4

0.33

MVP

0.39

ClinPred

0.053

GERP RS

3.2

Varity_R

0.19

gMVP

0.48

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