19-41848523-G-C

Variant names:

• chr19-41848523-G-C
• rs782574135
• NM_001040283.3:c.442G>C

Variant summary

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

The NM_001040283.3(DMRTC2):​c.442G>C​(p.Gly148Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000348 in 1,436,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: DMRTC2 NM_001040283.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.77

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=0.13367754).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMRTC2	NM_001040283.3	c.442G>C	p.Gly148Arg	missense_variant	Exon 4 of 9	ENST00000269945.8	NP_001035373.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMRTC2	ENST00000269945.8	c.442G>C	p.Gly148Arg	missense_variant	Exon 4 of 9	1	NM_001040283.3	ENSP00000269945.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000981 AC: 2 AN: 203976 Hom.: 0 AF XY: 0.00000907 AC XY: 1 AN XY: 110204

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000229

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000348 AC: 5 AN: 1436942 Hom.: 0 Cov.: 31 AF XY: 0.00000281 AC XY: 2 AN XY: 712934

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: 0.00000455

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	19
DANN	Benign	0.90
DEOGEN2	Benign	0.14	.;.;T;.
Eigen	Benign	-0.095
Eigen_PC	Benign	0.016
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.68	T;T;T;T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.6	.;.;L;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.66	.;.;N;.
REVEL	Benign	0.083
Sift	Benign	0.11	.;.;T;.
Sift4G	Benign	0.39	T;T;T;T
Polyphen		0.12, 0.048	.;B;B;.
Vest4		0.20, 0.17
MutPred		0.14		Gain of phosphorylation at S151 (P = 0.0831);Gain of phosphorylation at S151 (P = 0.0831);Gain of phosphorylation at S151 (P = 0.0831);Gain of phosphorylation at S151 (P = 0.0831);
MVP		0.043
MPC		0.24
ClinPred		0.30	T
GERP RS		4.6
Varity_R		0.18
gMVP		0.24

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

LitVar

Other links and lift over

dbSNP: rs782574135; hg19: chr19-42352591;