Variant 9-1051740-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_181872.6(DMRT2):c.127G>A(p.Asp43Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000724 in 1,381,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

DMRT2
NM_181872.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.15

Variant links:

Genes affected

DMRT2 (HGNC:2935): (doublesex and mab-3 related transcription factor 2) The protein encoded by this gene belongs to the DMRT gene family, sharing a DM DNA-binding domain with Drosophila 'doublesex' (dsx) and C. elegans mab3, genes involved in sex determination in these organisms. Also, this gene is located in a region of the human genome (chromosome 9p24.3) associated with gonadal dysgenesis and XY sex reversal. Hence this gene is one of the candidates for sex-determining gene(s) on chr 9. [provided by RefSeq, Apr 2010]

DMRT2 links:

DMRT2 (HGNC:):

DMRT2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.108751506).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMRT2	NM_181872.6 linkuse as main transcript	c.127G>A	p.Asp43Asn	missense_variant	2/4	ENST00000358146.7	NP_870987.2	Q9Y5R5-1Q05C20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMRT2	ENST00000358146.7 linkuse as main transcript	c.127G>A	p.Asp43Asn	missense_variant	2/4	1	NM_181872.6	ENSP00000350865.2		Q9Y5R5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.24e-7

AC:

AN:

1381004

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

681934

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000174

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 02, 2024

The c.127G>A (p.D43N) alteration is located in exon 2 (coding exon 1) of the DMRT2 gene. This alteration results from a G to A substitution at nucleotide position 127, causing the aspartic acid (D) at amino acid position 43 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.060

.;.;T;.;T;.

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.59

.;.;T;.;.;T

M_CAP

Uncertain

0.29

MetaRNN

Benign

0.11

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;L;L;L;L;L

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.21

.;N;N;N;N;N

REVEL

Benign

0.082

Sift

Benign

0.19

.;T;T;T;T;T

Sift4G

Uncertain

0.018

D;D;D;D;D;D

Polyphen

0.15

.;.;B;.;B;.

Vest4

0.11

MutPred

0.077

Gain of glycosylation at P41 (P = 0.1447);Gain of glycosylation at P41 (P = 0.1447);Gain of glycosylation at P41 (P = 0.1447);Gain of glycosylation at P41 (P = 0.1447);Gain of glycosylation at P41 (P = 0.1447);Gain of glycosylation at P41 (P = 0.1447);

MVP

0.33

MPC

0.0070

ClinPred

0.26

GERP RS

2.8

Varity_R

0.091

gMVP

0.053

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

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