2-27582145-A-G

Position:

• chr2-27582145-A-G

Variant summary

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

The NM_032266.5(C2orf16):​c.15785A>G​(p.Glu5262Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: C2orf16 NM_032266.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.145

Genes affected

C2orf16 (HGNC:25275): (SPATA31 subfamily H member 1) Located in extracellular exosome and nucleus. [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=0.10119492).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C2orf16	NM_032266.5	c.15785A>G	p.Glu5262Gly	missense_variant	5/5	ENST00000447166.3	NP_115642.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C2orf16	ENST00000447166.3	c.15785A>G	p.Glu5262Gly	missense_variant	5/5	3	NM_032266.5	ENSP00000403181	P1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151874 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 34

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151874 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74196

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2021

The c.5573A>G (p.E1858G) alteration is located in exon 1 (coding exon 1) of the C2orf16 gene. This alteration results from a A to G substitution at nucleotide position 5573, causing the glutamic acid (E) at amino acid position 1858 to be replaced by a glycine (G). 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	Benign	0.11
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	8.1
DANN	Benign	0.97
DEOGEN2	Benign	0.018	.;T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.33	T;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.5	.;L
MutationTaster	Benign	1.0	N
PROVEAN	Benign	-1.9	.;N
REVEL	Benign	0.052
Sift	Uncertain	0.010	.;D
Sift4G	Uncertain	0.060	.;T
Polyphen		0.84	.;P
Vest4		0.065
MutPred		0.21		.;Gain of MoRF binding (P = 0.0211);
MVP		0.13
MPC		0.10
ClinPred		0.20	T
GERP RS		2.3
Varity_R		0.12
gMVP		0.035

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: rs1427982668; hg19: chr2-27805012;