rs781959531

Variant names:

• chr19-41849252-C-A
• NM_001040283.3:c.751C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-41849252-C-A
• chr19-41849252-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001040283.3(DMRTC2):​c.751C>A​(p.Arg251Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. R251C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DMRTC2 NM_001040283.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.50

Genes affected

DMRTC2 (HGNC:13911): (DMRT like family C2) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in germ cell development; regulation of transcription by RNA polymerase II; and sex differentiation. Predicted to act upstream of or within male gamete generation and positive regulation of histone H3-K9 methylation. Predicted to be located in XY body. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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=0.13032404).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMRTC2	NM_001040283.3	c.751C>A	p.Arg251Ser	missense_variant	Exon 6 of 9	ENST00000269945.8	NP_001035373.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMRTC2	ENST00000269945.8	c.751C>A	p.Arg251Ser	missense_variant	Exon 6 of 9	1	NM_001040283.3	ENSP00000269945.2
DMRTC2	ENST00000596827.5	c.751C>A	p.Arg251Ser	missense_variant	Exon 6 of 8	2		ENSP00000469525.1
DMRTC2	ENST00000601660.5	n.*116C>A		non_coding_transcript_exon_variant	Exon 6 of 7	2		ENSP00000472159.1
DMRTC2	ENST00000601660.5	n.*116C>A		3_prime_UTR_variant	Exon 6 of 7	2		ENSP00000472159.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461608 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727118

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	.;T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.017
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.37	T;T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.46	.;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.62	.;N
REVEL	Benign	0.071
Sift	Benign	0.46	.;T
Sift4G	Benign	0.44	T;T
Polyphen		0.47	P;B
Vest4		0.47
MutPred		0.16		Loss of loop (P = 0.0022);Loss of loop (P = 0.0022);
MVP		0.18
MPC		0.24
ClinPred		0.33	T
GERP RS		5.3
Varity_R		0.18
gMVP		0.14

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-42353320;