chr19-41850346-C-G

Variant names:

• chr19-41850346-C-G
• rs145455346
• NM_001040283.3:c.790C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001040283.3(DMRTC2):​c.790C>G​(p.Pro264Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00005 in 1,519,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. P264S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000055 (0 hom.)
• Consequence: DMRTC2 NM_001040283.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.107390255).

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.790C>G	p.Pro264Ala	missense	Exon 7 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.790C>G	p.Pro264Ala	missense	Exon 7 of 9	ENSP00000269945.2	Q8IXT2-1
	DMRTC2	ENST00000596827.5	TSL:2	c.790C>G	p.Pro264Ala	missense	Exon 7 of 8	ENSP00000469525.1	B4DX56
	DMRTC2	ENST00000599022.1	TSL:3	n.103C>G		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152146 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000338 AC: 6 AN: 177560 AF XY: 0.0000321

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000474

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000578

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000548 AC: 75 AN: 1367598 Hom.: 0 Cov.: 31 AF XY: 0.0000492 AC XY: 33 AN XY: 670782

African (AFR) AF: 0.00 AC: 0 AN: 30014

American (AMR) AF: 0.0000337 AC: 1 AN: 29650

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20036

East Asian (EAS) AF: 0.00 AC: 0 AN: 38380

South Asian (SAS) AF: 0.00 AC: 0 AN: 70294

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50062

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5314

European-Non Finnish (NFE) AF: 0.0000656 AC: 70 AN: 1067568

Other (OTH) AF: 0.0000711 AC: 4 AN: 56280

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152146 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74334

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

American (AMR) AF: 0.00 AC: 0 AN: 15276

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000501 AC: 6

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	19
DANN	Benign	0.64
DEOGEN2	Benign	0.15	T
Eigen	Benign	0.024
Eigen_PC	Benign	0.056
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PhyloP100		1.4
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.038
Sift	Benign	0.042	D
Sift4G	Benign	0.11	T
Polyphen		1.0	D
Vest4		0.36
MVP		0.068
MPC		0.24
ClinPred		0.11	T
GERP RS		3.8
Varity_R		0.050
gMVP		0.088
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs145455346; hg19: chr19-42354414;