19-41848969-T-G

Variant names:

• chr19-41848969-T-G
• NM_001040283.3:c.622T>G

Variant summary

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

The NM_001040283.3(DMRTC2):​c.622T>G​(p.Phe208Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DMRTC2 NM_001040283.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.31
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040283.3. 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
	DMRTC2	NM_001040283.3	MANE Select	c.622T>G	p.Phe208Val	missense	Exon 5 of 9	NP_001035373.1	Q8IXT2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMRTC2	ENST00000269945.8	TSL:1 MANE Select	c.622T>G	p.Phe208Val	missense	Exon 5 of 9	ENSP00000269945.2	Q8IXT2-1
	DMRTC2	ENST00000596827.5	TSL:2	c.622T>G	p.Phe208Val	missense	Exon 5 of 8	ENSP00000469525.1	B4DX56
	DMRTC2	ENST00000601660.5	TSL:2	n.662T>G		non_coding_transcript_exon	Exon 5 of 7	ENSP00000472159.1	Q8IXT2-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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	Uncertain	0.36
BayesDel_addAF	Benign	-0.0082	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.047	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		2.3
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.17
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.39	T
Polyphen		1.0	D
Vest4		0.60
MutPred		0.15		Gain of glycosylation at S204 (P = 0.0925)
MVP		0.22
MPC		0.49
ClinPred		0.95	D
GERP RS		5.3
Varity_R		0.34
gMVP		0.42
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr19-42353037;