NM_001144994.2:c.352G>T

Variant names:

• chr2-231037917-G-T
• rs1356081426
• NM_001144994.2:c.352G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001144994.2(C2orf72):​c.352G>T​(p.Ala118Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000114 in 880,172 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. 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. A118T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: C2orf72 NM_001144994.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.480

Genes affected

C2orf72 (HGNC:27418): (chromosome 2 open reading frame 72)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.031157374).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C2orf72	NM_001144994.2	c.352G>T	p.Ala118Ser	missense_variant	Exon 1 of 3	ENST00000373640.5	NP_001138466.1
C2orf72	XM_047443876.1	c.352G>T	p.Ala118Ser	missense_variant	Exon 1 of 3		XP_047299832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C2orf72	ENST00000373640.5	c.352G>T	p.Ala118Ser	missense_variant	Exon 1 of 3	2	NM_001144994.2	ENSP00000362743.4
C2orf72	ENST00000477463.1	n.100+256G>T		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000114 AC: 1 AN: 880172 Hom.: 0 Cov.: 32 AF XY: 0.00000240 AC XY: 1 AN XY: 416730

African (AFR) AF: 0.00 AC: 0 AN: 16450

American (AMR) AF: 0.00 AC: 0 AN: 4762

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6614

East Asian (EAS) AF: 0.00 AC: 0 AN: 4710

South Asian (SAS) AF: 0.0000445 AC: 1 AN: 22454

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1770

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 792510

Other (OTH) AF: 0.00 AC: 0 AN: 29276

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	18
DANN	Benign	0.92
DEOGEN2	Benign	0.0024	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.45	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.26	N
PhyloP100		0.48
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.024
Sift	Benign	0.86	T
Sift4G	Benign	0.21	T
Polyphen		0.041	B
Vest4		0.070
MutPred		0.21		Gain of relative solvent accessibility (P = 0.0082);
MVP		0.014
ClinPred		0.10	T
GERP RS		-0.34
PromoterAI		0.012	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		3.5
Varity_R		0.037
gMVP		0.089
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

Publications

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Other links and lift over

dbSNP: rs1356081426; hg19: chr2-231902632;