15-29151746-A-G

Position:

• chr15-29151746-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_015307.2(ENTREP2):​c.618T>C​(p.Asp206=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0751 in 1,551,226 control chromosomes in the GnomAD database, including 8,548 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (3112 hom., cov: 33)
  • Exomes 𝑓: 0.067 (5436 hom.)
• Consequence: ENTREP2 NM_015307.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.258

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=0.258 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENTREP2	NM_015307.2	c.618T>C	p.Asp206=	synonymous_variant	5/11	ENST00000261275.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENTREP2	ENST00000261275.5	c.618T>C	p.Asp206=	synonymous_variant	5/11	5	NM_015307.2	P1
ENTREP2	ENST00000560021.1	n.354T>C		non_coding_transcript_exon_variant	2/8	1

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22600 AN: 152054 Hom.: 3099 Cov.: 33

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.0328

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.0897

Gnomad FIN AF: 0.0419

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0504

Gnomad OTH AF: 0.140

GnomAD3 exomes AF: 0.0931 AC: 14680 AN: 157630 Hom.: 1199 AF XY: 0.0859 AC XY: 7150 AN XY: 83192

Gnomad AFR exome AF: 0.369

Gnomad AMR exome AF: 0.143

Gnomad ASJ exome AF: 0.0315

Gnomad EAS exome AF: 0.180

Gnomad SAS exome AF: 0.0787

Gnomad FIN exome AF: 0.0396

Gnomad NFE exome AF: 0.0499

Gnomad OTH exome AF: 0.0836

GnomAD4 exome AF: 0.0671 AC: 93823 AN: 1399054 Hom.: 5436 Cov.: 31 AF XY: 0.0661 AC XY: 45632 AN XY: 690028

Gnomad4 AFR exome AF: 0.376

Gnomad4 AMR exome AF: 0.138

Gnomad4 ASJ exome AF: 0.0344

Gnomad4 EAS exome AF: 0.177

Gnomad4 SAS exome AF: 0.0774

Gnomad4 FIN exome AF: 0.0413

Gnomad4 NFE exome AF: 0.0520

Gnomad4 OTH exome AF: 0.0889

GnomAD4 genome AF: 0.149 AC: 22656 AN: 152172 Hom.: 3112 Cov.: 33 AF XY: 0.146 AC XY: 10866 AN XY: 74398

Gnomad4 AFR AF: 0.363

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.0328

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.0902

Gnomad4 FIN AF: 0.0419

Gnomad4 NFE AF: 0.0505

Gnomad4 OTH AF: 0.144

Alfa AF: 0.0842 Hom.: 1130

Bravo AF: 0.170

Asia WGS AF: 0.179 AC: 621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	1.2
DANN	Benign	0.50

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: rs3764211; hg19: chr15-29443949; COSMIC: COSV54265467;