NM_032110.3:c.706G>A

Variant names:

• chr1-50419588-C-T
• rs746793380
• NM_032110.3:c.706G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032110.3(DMRTA2):​c.706G>A​(p.Gly236Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000286 in 1,400,290 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: 33)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: DMRTA2 NM_032110.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.57
• Publications: 0 publications found

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]

FAF1-AS1 (HGNC:40228): (FAF1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26710933).

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.706G>A	p.Gly236Ser	missense	Exon 3 of 3	NP_115486.1	Q96SC8
	DMRTA2	NM_001437821.1		c.706G>A	p.Gly236Ser	missense	Exon 2 of 2	NP_001424750.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMRTA2	ENST00000404795.4	TSL:5 MANE Select	c.706G>A	p.Gly236Ser	missense	Exon 3 of 3	ENSP00000383909.3	Q96SC8
	DMRTA2	ENST00000418121.5	TSL:1	c.706G>A	p.Gly236Ser	missense	Exon 2 of 2	ENSP00000399370.1	Q96SC8
	DMRTA2	ENST00000948348.1		c.706G>A	p.Gly236Ser	missense	Exon 3 of 3	ENSP00000618407.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000286 AC: 4 AN: 1400290 Hom.: 0 Cov.: 35 AF XY: 0.00000289 AC XY: 2 AN XY: 691266

African (AFR) AF: 0.00 AC: 0 AN: 30046

American (AMR) AF: 0.00 AC: 0 AN: 36920

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23320

East Asian (EAS) AF: 0.00 AC: 0 AN: 36788

South Asian (SAS) AF: 0.00 AC: 0 AN: 78012

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5536

European-Non Finnish (NFE) AF: 0.00000370 AC: 4 AN: 1082464

Other (OTH) AF: 0.00 AC: 0 AN: 57586

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.023	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.59	N
PhyloP100		6.6
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.16
Sift	Benign	0.31	T
Sift4G	Benign	0.43	T
Polyphen		1.0	D
Vest4		0.33
MutPred		0.22		Gain of phosphorylation at G236 (P = 0.0012)
MVP		0.17
ClinPred		0.94	D
GERP RS		4.0
Varity_R		0.15
gMVP		0.31
Mutation Taster		=77/23	polymorphism

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

Other links and lift over

dbSNP: rs746793380; hg19: chr1-50885260; COSMIC: COSV108243327; COSMIC: COSV108243327;