chr2-74415209-C-A

Variant names:

• chr2-74415209-C-A
• rs747454015
• NM_001316764.3:c.968G>T

Variant summary

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

The NM_001316764.3(C2orf81):​c.968G>T​(p.Gly323Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 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. G323E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: C2orf81 NM_001316764.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.959
• Publications: 0 publications found

Genes affected

C2orf81 (HGNC:34350): (chromosome 2 open reading frame 81) Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000159239 (HGNC:):

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=0.16050524).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001316764.3. 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
	C2orf81	NM_001316764.3	MANE Select	c.968G>T	p.Gly323Val	missense	Exon 3 of 3	NP_001303693.1	A0A804HJ35
	C2orf81	NM_001145054.2		c.887G>T	p.Gly296Val	missense	Exon 4 of 4	NP_001138526.1	G3XAA6
	C2orf81	NM_001316765.2		c.821G>T	p.Gly274Val	missense	Exon 3 of 3	NP_001303694.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C2orf81	ENST00000684111.1	MANE Select	c.968G>T	p.Gly323Val	missense	Exon 3 of 3	ENSP00000507340.1	A0A804HJ35
	ENSG00000159239	ENST00000517883.2	TSL:5	n.683G>T		non_coding_transcript_exon	Exon 2 of 5	ENSP00000431103.2	E5RJQ4
	C2orf81	ENST00000290390.9	TSL:5	c.887G>T	p.Gly296Val	missense	Exon 4 of 4	ENSP00000290390.5	G3XAA6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398094 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 689552

African (AFR) AF: 0.00 AC: 0 AN: 31562

American (AMR) AF: 0.00 AC: 0 AN: 35630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25130

East Asian (EAS) AF: 0.00 AC: 0 AN: 35692

South Asian (SAS) AF: 0.00 AC: 0 AN: 79168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078662

Other (OTH) AF: 0.00 AC: 0 AN: 57968

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	11
DANN	Uncertain	0.99
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.96
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.025
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.053	T
Polyphen		0.97	D
Vest4		0.11
MutPred		0.37		Loss of disorder (P = 0.0728)
MVP		0.29
ClinPred		0.82	D
GERP RS		-0.96
Varity_R		0.030
gMVP		0.088
Mutation Taster		=99/1	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: rs747454015; hg19: chr2-74642336;