15-29123601-C-G

Variant names:

• chr15-29123601-C-G
• rs747245338
• NM_015307.2:c.1358G>C

Variant summary

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

The NM_015307.2(ENTREP2):​c.1358G>C​(p.Gly453Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,399,316 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. G453E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: ENTREP2 NM_015307.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.93
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08079752).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENTREP2	NM_015307.2	c.1358G>C	p.Gly453Ala	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.1358G>C	p.Gly453Ala	missense_variant	Exon 11 of 11	5	NM_015307.2	ENSP00000261275.4
ENTREP2	ENST00000560021.1	n.1094G>C		non_coding_transcript_exon_variant	Exon 8 of 8	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000164 AC: 23 AN: 1399316 Hom.: 0 Cov.: 35 AF XY: 0.0000174 AC XY: 12 AN XY: 690152

African (AFR) AF: 0.00 AC: 0 AN: 31596

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: 35732

South Asian (SAS) AF: 0.00 AC: 0 AN: 79228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49280

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

European-Non Finnish (NFE) AF: 0.0000204 AC: 22 AN: 1078892

Other (OTH) AF: 0.0000172 AC: 1 AN: 58004

GnomAD4 genome Cov.: 33

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	19
DANN	Benign	0.87
DEOGEN2	Benign	0.0038	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.9
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.095
Sift	Benign	0.29	T
Sift4G	Benign	0.35	T
Polyphen		0.024	B
Vest4		0.068
MutPred		0.16		Loss of catalytic residue at A452 (P = 0.0869);
MVP		0.014
ClinPred		0.093	T
GERP RS		3.4
Varity_R		0.049
gMVP		0.098
Mutation Taster		=90/10	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: rs747245338; hg19: chr15-29415804;