Genetic Variant DMRTA2:p.Asp369Glu (chr1-50419187-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032110.3(DMRTA2):c.1107T>A(p.Asp369Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DMRTA2
NM_032110.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.577

Publications

0 publications found

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:

FAF1-AS1 (HGNC:40228): (FAF1 antisense RNA 1)

FAF1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.049287528).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032110.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMRTA2	NM_032110.3	MANE Select	c.1107T>A	p.Asp369Glu	missense	Exon 3 of 3	NP_115486.1	Q96SC8
	DMRTA2	NM_001437821.1		c.1107T>A	p.Asp369Glu	missense	Exon 2 of 2	NP_001424750.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DMRTA2	ENST00000404795.4	TSL:5 MANE Select	c.1107T>A	p.Asp369Glu	missense	Exon 3 of 3	ENSP00000383909.3	Q96SC8
DMRTA2	ENST00000418121.5	TSL:1	c.1107T>A	p.Asp369Glu	missense	Exon 2 of 2	ENSP00000399370.1	Q96SC8
DMRTA2	ENST00000948348.1		c.1107T>A	p.Asp369Glu	missense	Exon 3 of 3	ENSP00000618407.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1175526

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

569578

African (AFR)

AF:

0.00

AC:

AN:

23752

American (AMR)

AF:

0.00

AC:

AN:

10756

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14844

East Asian (EAS)

AF:

0.00

AC:

AN:

25518

South Asian (SAS)

AF:

0.00

AC:

AN:

51190

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25112

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3302

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

974122

Other (OTH)

AF:

0.00

AC:

AN:

46930

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.78

CADD

Benign

2.7

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.013

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.37

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.049

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

PhyloP100

-0.58

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.39

REVEL

Benign

0.028

Sift

Benign

0.22

Sift4G

Benign

0.17

Polyphen

0.0

Vest4

0.042

MutPred

0.14

Gain of glycosylation at K370 (P = 0.1871)

MVP

0.030

ClinPred

0.048

GERP RS

-1.5

Varity_R

0.043

gMVP

0.18

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over