chr1-50419510-T-C

Position:

• chr1-50419510-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032110.3(DMRTA2):​c.784A>G​(p.Ser262Gly) 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. 14/20 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)
• Consequence: DMRTA2 NM_032110.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.82

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05644706).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMRTA2	NM_032110.3	c.784A>G	p.Ser262Gly	missense_variant	3/3	ENST00000404795.4	NP_115486.1
DMRTA2	XM_011541937.3	c.784A>G	p.Ser262Gly	missense_variant	2/2		XP_011540239.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMRTA2	ENST00000404795.4	c.784A>G	p.Ser262Gly	missense_variant	3/3	5	NM_032110.3	ENSP00000383909.3
DMRTA2	ENST00000418121.5	c.784A>G	p.Ser262Gly	missense_variant	2/2	1		ENSP00000399370.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.036	T;T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.55	.;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.056	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.35	N;N
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.054
Sift	Benign	0.35	T;T
Sift4G	Benign	0.41	T;T
Polyphen		0.0	B;B
Vest4		0.20
MutPred		0.23		Loss of glycosylation at S262 (P = 0.0042);Loss of glycosylation at S262 (P = 0.0042);
MVP		0.061
ClinPred		0.14	T
GERP RS		2.6
Varity_R		0.17
gMVP		0.23

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

Other links and lift over

dbSNP: rs1572734214; hg19: chr1-50885182;