2-70160694-C-T

Variant names:

• chr2-70160694-C-T
• NM_017880.3:c.1447G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017880.3(C2orf42):​c.1447G>A​(p.Glu483Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: C2orf42 NM_017880.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.04

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38699692).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C2orf42	NM_017880.3	c.1447G>A	p.Glu483Lys	missense_variant	Exon 9 of 10	ENST00000264434.7	NP_060350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C2orf42	ENST00000264434.7	c.1447G>A	p.Glu483Lys	missense_variant	Exon 9 of 10	1	NM_017880.3	ENSP00000264434.2
C2orf42	ENST00000420306.1	c.1447G>A	p.Glu483Lys	missense_variant	Exon 7 of 8	2		ENSP00000404515.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461250 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726978

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 09, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1447G>A (p.E483K) alteration is located in exon 9 (coding exon 7) of the C2orf42 gene. This alteration results from a G to A substitution at nucleotide position 1447, causing the glutamic acid (E) at amino acid position 483 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.32
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0076	T;T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.85	.;D
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.39	T;T
MetaSVM	Uncertain	0.70	D
MutationAssessor	Benign	1.6	L;L
PROVEAN	Benign	-1.0	N;N
REVEL	Uncertain	0.63
Sift	Benign	0.21	T;T
Sift4G	Benign	0.53	T;T
Polyphen		0.97	D;D
Vest4		0.41
MutPred		0.34		Gain of ubiquitination at E483 (P = 0.0192);Gain of ubiquitination at E483 (P = 0.0192);
MVP		0.61
MPC		0.34
ClinPred		0.86	D
GERP RS		5.2
Varity_R		0.20
gMVP		0.53

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-70387826;