Variant 1-50419106-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_032110.3(DMRTA2):c.1188C>T(p.Ala396Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.882 in 145,400 control chromosomes in the GnomAD database, including 55,559 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.88 ( 55559 hom., cov: 32)

Exomes 𝑓: 0.84 ( 332276 hom. )

Failed GnomAD Quality Control

Consequence

DMRTA2
NM_032110.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.482

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 1-50419106-G-A is Benign according to our data. Variant chr1-50419106-G-A is described in ClinVar as [Benign]. Clinvar id is 1337081.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.482 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMRTA2	NM_032110.3 linkuse as main transcript	c.1188C>T	p.Ala396Ala	synonymous_variant	3/3	ENST00000404795.4	NP_115486.1	Q96SC8
DMRTA2	XM_011541937.3 linkuse as main transcript	c.1188C>T	p.Ala396Ala	synonymous_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.1188C>T	p.Ala396Ala	synonymous_variant	3/3	5	NM_032110.3	ENSP00000383909.3		Q96SC8
DMRTA2	ENST00000418121.5 linkuse as main transcript	c.1188C>T	p.Ala396Ala	synonymous_variant	2/2	1		ENSP00000399370.1		Q96SC8

Frequencies

GnomAD3 genomes

AF:

0.882

AC:

128164

AN:

145312

Hom.:

55510

Cov.:

show subpopulations

Gnomad AFR

AF:

0.952

Gnomad AMI

AF:

0.855

Gnomad AMR

AF:

0.890

Gnomad ASJ

AF:

0.818

Gnomad EAS

AF:

0.830

Gnomad SAS

AF:

0.837

Gnomad FIN

AF:

0.888

Gnomad MID

AF:

0.878

Gnomad NFE

AF:

0.846

Gnomad OTH

AF:

0.875

GnomAD3 exomes

AF:

0.799

AC:

326

AN:

408

Hom.:

132

AF XY:

0.802

AC XY:

207

AN XY:

258

show subpopulations

Gnomad AMR exome

AF:

1.00

Gnomad ASJ exome

AF:

0.667

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

0.785

Gnomad OTH exome

AF:

0.900

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.842

AC:

811398

AN:

963120

Hom.:

332276

Cov.:

AF XY:

0.842

AC XY:

385130

AN XY:

457418

show subpopulations

Gnomad4 AFR exome

AF:

0.956

Gnomad4 AMR exome

AF:

0.910

Gnomad4 ASJ exome

AF:

0.821

Gnomad4 EAS exome

AF:

0.839

Gnomad4 SAS exome

AF:

0.827

Gnomad4 FIN exome

AF:

0.889

Gnomad4 NFE exome

AF:

0.839

Gnomad4 OTH exome

AF:

0.845

GnomAD4 genome

AF:

0.882

AC:

128257

AN:

145400

Hom.:

55559

Cov.:

AF XY:

0.882

AC XY:

62588

AN XY:

70952

show subpopulations

Gnomad4 AFR

AF:

0.952

Gnomad4 AMR

AF:

0.890

Gnomad4 ASJ

AF:

0.818

Gnomad4 EAS

AF:

0.830

Gnomad4 SAS

AF:

0.837

Gnomad4 FIN

AF:

0.888

Gnomad4 NFE

AF:

0.846

Gnomad4 OTH

AF:

0.873

Alfa

AF:

0.861

Hom.:

3878

ClinVar

Significance: 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

May 30, 2018

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

1.9

DANN

Benign

0.93

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