2-70179608-G-T

Variant names:

• chr2-70179608-G-T
• rs372665510
• NM_017880.3:c.858C>A

Variant summary

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

The NM_017880.3(C2orf42):​c.858C>A​(p.Cys286*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,387,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: C2orf42 NM_017880.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63
• Publications: 0 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 2 ACMG points.

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

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.858C>A	p.Cys286*	stop_gained	Exon 4 of 10	NP_060350.1	Q9NWW7
	C2orf42	NM_001348758.2		c.858C>A	p.Cys286*	stop_gained	Exon 4 of 10	NP_001335687.1	Q9NWW7
	C2orf42	NM_001348759.2		c.858C>A	p.Cys286*	stop_gained	Exon 4 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.858C>A	p.Cys286*	stop_gained	Exon 4 of 10	ENSP00000264434.2	Q9NWW7
	C2orf42	ENST00000884989.1		c.858C>A	p.Cys286*	stop_gained	Exon 4 of 11	ENSP00000555048.1
	C2orf42	ENST00000967691.1		c.858C>A	p.Cys286*	stop_gained	Exon 2 of 9	ENSP00000637750.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1387832 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 695028

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32056

American (AMR) AF: 0.00 AC: 0 AN: 44406

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25514

East Asian (EAS) AF: 0.00 AC: 0 AN: 39312

South Asian (SAS) AF: 0.00 AC: 0 AN: 84272

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53112

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5616

European-Non Finnish (NFE) AF: 0.00000191 AC: 2 AN: 1045726

Other (OTH) AF: 0.00 AC: 0 AN: 57818

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000000983081), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.55	D
BayesDel_noAF	Pathogenic	0.55
CADD	Pathogenic	37
DANN	Uncertain	0.99
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.83	D
PhyloP100		1.6
Vest4		0.41
GERP RS		2.1
Mutation Taster		=8/192	disease causing (fs/PTC)

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: rs372665510; hg19: chr2-70406740;