chr2-70150447-C-A

Variant names:

• chr2-70150447-C-A
• rs1238260696
• NM_017880.3:c.1634G>T

Variant summary

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

The NM_017880.3(C2orf42):​c.1634G>T​(p.Arg545Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: C2orf42 NM_017880.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.98

Genes affected

C2orf42 (HGNC:26056): (chromosome 2 open reading frame 42) Located in nucleoplasm. [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=0.21428818).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C2orf42	NM_017880.3	c.1634G>T	p.Arg545Leu	missense_variant	Exon 10 of 10	ENST00000264434.7	NP_060350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C2orf42	ENST00000264434.7	c.1634G>T	p.Arg545Leu	missense_variant	Exon 10 of 10	1	NM_017880.3	ENSP00000264434.2
C2orf42	ENST00000420306.1	c.1634G>T	p.Arg545Leu	missense_variant	Exon 8 of 8	2		ENSP00000404515.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T;T
Eigen	Benign	0.074
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.89	.;D
M_CAP	Uncertain	0.097	D
MetaRNN	Benign	0.21	T;T
MetaSVM	Uncertain	0.18	D
MutationAssessor	Benign	1.7	L;L
PROVEAN	Benign	-2.3	N;N
REVEL	Uncertain	0.54
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.029	D;D
Polyphen		0.16	B;B
Vest4		0.46
MutPred		0.38		Loss of methylation at R545 (P = 0.0245);Loss of methylation at R545 (P = 0.0245);
MVP		0.58
MPC		0.92
ClinPred		0.87	D
GERP RS		5.8
Varity_R		0.23
gMVP		0.64

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: rs1238260696; hg19: chr2-70377579;