NM_015307.2:c.1481C>G

Variant names:

• chr15-29123478-G-C
• rs1023189113
• NM_015307.2:c.1481C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015307.2(ENTREP2):​c.1481C>G​(p.Ala494Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. A494V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ENTREP2 NM_015307.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.63
• Publications: 0 publications found

Genes affected

ENTREP2 (HGNC:29075): (endosomal transmembrane epsin interactor 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3603039).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENTREP2	NM_015307.2	c.1481C>G	p.Ala494Gly	missense_variant	Exon 11 of 11	ENST00000261275.5	NP_056122.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENTREP2	ENST00000261275.5	c.1481C>G	p.Ala494Gly	missense_variant	Exon 11 of 11	5	NM_015307.2	ENSP00000261275.4
ENTREP2	ENST00000560021.1	n.1217C>G		non_coding_transcript_exon_variant	Exon 8 of 8	1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399366 Hom.: 0 Cov.: 72 AF XY: 0.00000145 AC XY: 1 AN XY: 690190

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49244

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078958

Other (OTH) AF: 0.00 AC: 0 AN: 58012

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		7.6
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.19
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.68	P
Vest4		0.46
MutPred		0.44		Loss of ubiquitination at K495 (P = 0.051);
MVP		0.092
ClinPred		0.98	D
GERP RS		4.4
Varity_R		0.15
gMVP		0.12
Mutation Taster		=59/41	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1023189113; hg19: chr15-29415681;