Genetic Variant NM_032110.3:c.28G>C (chr1-50421509-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_032110.3(DMRTA2):c.28G>C(p.Val10Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000535 in 1,271,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

DMRTA2
NM_032110.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.01

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.

BP4

Computational evidence support a benign effect (MetaRNN=0.09354597).

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.28G>C	p.Val10Leu	missense	Exon 2 of 3	NP_115486.1	Q96SC8
	DMRTA2	NM_001437821.1		c.28G>C	p.Val10Leu	missense	Exon 1 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.28G>C	p.Val10Leu	missense	Exon 2 of 3	ENSP00000383909.3	Q96SC8
DMRTA2	ENST00000418121.5	TSL:1	c.28G>C	p.Val10Leu	missense	Exon 1 of 2	ENSP00000399370.1	Q96SC8
DMRTA2	ENST00000948348.1		c.28G>C	p.Val10Leu	missense	Exon 2 of 3	ENSP00000618407.1

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000554

AC:

AN:

1119466

Hom.:

Cov.:

AF XY:

0.0000617

AC XY:

AN XY:

534708

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22992

American (AMR)

AF:

0.00

AC:

AN:

8972

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15004

East Asian (EAS)

AF:

0.00206

AC:

AN:

26642

South Asian (SAS)

AF:

0.00

AC:

AN:

26562

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23554

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3118

European-Non Finnish (NFE)

AF:

0.00000106

AC:

AN:

947190

Other (OTH)

AF:

0.000132

AC:

AN:

45432

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000395

AC:

AN:

152072

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41438

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00116

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10560

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68002

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000491

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

0.23

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.50

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.017

Eigen

Benign

-0.026

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.58

M_CAP

Benign

0.078

MetaRNN

Benign

0.094

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

PhyloP100

1.0

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.52

REVEL

Benign

0.080

Sift

Uncertain

0.028

Sift4G

Benign

0.32

Polyphen

0.49

Vest4

0.16

MutPred

0.12

Gain of helix (P = 0.0854)

MVP

0.081

ClinPred

0.51

GERP RS

4.7

PromoterAI

0.055

Neutral

(source)

Varity_R

0.24

gMVP

0.56

Mutation Taster

=91/9

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over