1-50419588-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032110.3(DMRTA2):​c.706G>C​(p.Gly236Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000714 in 1,400,290 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G236S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: DMRTA2 NM_032110.3 missense
• Clinical Significance: Not reported in ClinVar
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2468962).

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>C	p.Gly236Arg	missense	Exon 3 of 3	NP_115486.1	Q96SC8
	DMRTA2	NM_001437821.1		c.706G>C	p.Gly236Arg	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>C	p.Gly236Arg	missense	Exon 3 of 3	ENSP00000383909.3	Q96SC8
	DMRTA2	ENST00000418121.5	TSL:1	c.706G>C	p.Gly236Arg	missense	Exon 2 of 2	ENSP00000399370.1	Q96SC8
	DMRTA2	ENST00000948348.1		c.706G>C	p.Gly236Arg	missense	Exon 3 of 3	ENSP00000618407.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000564 AC: 1 AN: 177428 AF XY: 0.0000101

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000746

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1400290 Hom.: 0 Cov.: 35 AF XY: 0.00000145 AC XY: 1 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: 0.0000272 AC: 1 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: 0.00 AC: 0 AN: 1082464

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

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.00000837 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		6.6
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.13
Sift	Benign	0.031	D
Sift4G	Benign	0.18	T
Polyphen		0.91	P
Vest4		0.41
MutPred		0.31		Gain of solvent accessibility (P = 0.0037)
MVP		0.30
ClinPred		0.74	D
GERP RS		4.0
Varity_R		0.30
gMVP		0.37
Mutation Taster		=66/34	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;