19-41850561-C-T

Position:

• chr19-41850561-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001040283.3(DMRTC2):​c.852C>T​(p.Gly284=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 1,612,916 control chromosomes in the GnomAD database, including 207,434 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.41 (14767 hom., cov: 31)
  • Exomes 𝑓: 0.51 (192667 hom.)
• Consequence: DMRTC2 NM_001040283.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.539

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP7: Synonymous conserved (PhyloP=0.539 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMRTC2	NM_001040283.3	c.852C>T	p.Gly284=	synonymous_variant	8/9	ENST00000269945.8	NP_001035373.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMRTC2	ENST00000269945.8	c.852C>T	p.Gly284=	synonymous_variant	8/9	1	NM_001040283.3	ENSP00000269945	P1
DMRTC2	ENST00000596827.5	c.1005C>T	p.Gly335=	synonymous_variant	7/8	2		ENSP00000469525
DMRTC2	ENST00000599022.1	n.318C>T		non_coding_transcript_exon_variant	1/2	3
DMRTC2	ENST00000601660.5	c.*370C>T		3_prime_UTR_variant, NMD_transcript_variant	7/7	2		ENSP00000472159

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62187 AN: 151884 Hom.: 14767 Cov.: 31

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.550

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.444

GnomAD4 exome AF: 0.510 AC: 744362 AN: 1460914 Hom.: 192667 Cov.: 69 AF XY: 0.513 AC XY: 372584 AN XY: 726730

Gnomad4 AFR exome AF: 0.140

Gnomad4 AMR exome AF: 0.492

Gnomad4 ASJ exome AF: 0.532

Gnomad4 EAS exome AF: 0.445

Gnomad4 SAS exome AF: 0.573

Gnomad4 FIN exome AF: 0.499

Gnomad4 NFE exome AF: 0.519

Gnomad4 OTH exome AF: 0.492

GnomAD4 genome AF: 0.409 AC: 62184 AN: 152002 Hom.: 14767 Cov.: 31 AF XY: 0.411 AC XY: 30507 AN XY: 74288

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.484

Gnomad4 ASJ AF: 0.523

Gnomad4 EAS AF: 0.440

Gnomad4 SAS AF: 0.557

Gnomad4 FIN AF: 0.481

Gnomad4 NFE AF: 0.519

Gnomad4 OTH AF: 0.440

Alfa AF: 0.502 Hom.: 23146

Bravo AF: 0.395

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2305809; hg19: chr19-42354629;