NM_017880.3:c.1634G>T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R545Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: C2orf42 NM_017880.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.98
• Publications: 2 publications found

Genes affected

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017880.3. 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
	C2orf42	NM_017880.3	MANE Select	c.1634G>T	p.Arg545Leu	missense	Exon 10 of 10	NP_060350.1	Q9NWW7
	C2orf42	NM_001348758.2		c.1634G>T	p.Arg545Leu	missense	Exon 10 of 10	NP_001335687.1	Q9NWW7
	C2orf42	NM_001348759.2		c.1634G>T	p.Arg545Leu	missense	Exon 10 of 10	NP_001335688.1	Q9NWW7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C2orf42	ENST00000264434.7	TSL:1 MANE Select	c.1634G>T	p.Arg545Leu	missense	Exon 10 of 10	ENSP00000264434.2	Q9NWW7
	C2orf42	ENST00000884989.1		c.1688G>T	p.Arg563Leu	missense	Exon 11 of 11	ENSP00000555048.1
	C2orf42	ENST00000967691.1		c.1688G>T	p.Arg563Leu	missense	Exon 9 of 9	ENSP00000637750.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Uncertain	0.18	D
MutationAssessor	Benign	1.7	L
PhyloP100		4.0
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.54
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.029	D
Polyphen		0.16	B
Vest4		0.46
MutPred		0.38		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
Mutation Taster		=76/24	polymorphism

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

Other links and lift over

dbSNP: rs1238260696; hg19: chr2-70377579;