Variant 9-1051684-A-C 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.71A>C(p.Glu24Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000707 in 1,414,386 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

DMRT2
NM_181872.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.84

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=0.18761641).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMRT2	NM_181872.6 linkuse as main transcript	c.71A>C	p.Glu24Ala	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.71A>C	p.Glu24Ala	missense_variant	2/4	1	NM_181872.6	ENSP00000350865.2		Q9Y5R5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000583

AC:

AN:

171516

Hom.:

AF XY:

0.0000105

AC XY:

AN XY:

95486

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000393

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.07e-7

AC:

AN:

1414386

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

701528

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:

0.0000122

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000872

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Gonadal agenesis

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Dept. of Cytogenetics, ICMR- National Institute of Immunohaematology

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.10

.;.;T;.;T;.

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.054

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.60

.;.;T;.;.;T

M_CAP

Pathogenic

0.48

MetaRNN

Benign

0.19

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;M;M;M;M;M

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.55

.;N;N;N;N;N

REVEL

Benign

0.076

Sift

Uncertain

0.0010

.;D;D;D;D;D

Sift4G

Benign

0.12

T;T;T;T;T;T

Polyphen

0.30

.;.;B;.;B;.

Vest4

0.20

MutPred

0.11

Loss of phosphorylation at S19 (P = 0.1688);Loss of phosphorylation at S19 (P = 0.1688);Loss of phosphorylation at S19 (P = 0.1688);Loss of phosphorylation at S19 (P = 0.1688);Loss of phosphorylation at S19 (P = 0.1688);Loss of phosphorylation at S19 (P = 0.1688);

MVP

0.72

MPC

0.0069

ClinPred

0.59

GERP RS

4.8

Varity_R

0.070

gMVP

0.078

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