1-50421467-G-T

Variant names:

• chr1-50421467-G-T
• rs1167876869
• NM_032110.3:c.70C>A

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.70C>A​(p.Pro24Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,964 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: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DMRTA2 NM_032110.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.796
• 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=0.20022187).

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.70C>A	p.Pro24Thr	missense	Exon 2 of 3	NP_115486.1	Q96SC8
	DMRTA2	NM_001437821.1		c.70C>A	p.Pro24Thr	missense	Exon 1 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.70C>A	p.Pro24Thr	missense	Exon 2 of 3	ENSP00000383909.3	Q96SC8
	DMRTA2	ENST00000418121.5	TSL:1	c.70C>A	p.Pro24Thr	missense	Exon 1 of 2	ENSP00000399370.1	Q96SC8
	DMRTA2	ENST00000948348.1		c.70C>A	p.Pro24Thr	missense	Exon 2 of 3	ENSP00000618407.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151964 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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

GnomAD2 exomes AF: 0.00 AC: 0 AN: 3328 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1136992 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 544800

African (AFR) AF: 0.00 AC: 0 AN: 23174

American (AMR) AF: 0.00 AC: 0 AN: 8964

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15234

East Asian (EAS) AF: 0.00 AC: 0 AN: 26920

South Asian (SAS) AF: 0.00 AC: 0 AN: 31212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 956520

Other (OTH) AF: 0.00 AC: 0 AN: 46242

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151964 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74222

African (AFR) AF: 0.00 AC: 0 AN: 41424

American (AMR) AF: 0.0000655 AC: 1 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10524

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67944

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

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	0.089
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	24
DANN	Uncertain	0.97
DEOGEN2	Benign	0.038	T
Eigen	Benign	-0.087
Eigen_PC	Benign	-0.068
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.57	T
M_CAP	Pathogenic	0.32	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.80
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.047
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.029	D
Polyphen		0.90	P
Vest4		0.21
MutPred		0.28		Gain of glycosylation at P24 (P = 0.0132)
MVP		0.12
ClinPred		0.24	T
GERP RS		3.7
PromoterAI		-0.078	Neutral
Varity_R		0.27
gMVP		0.57
Mutation Taster		=84/16	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: rs1167876869; hg19: chr1-50887139;