Variant 19-53050203-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001191055.2(ERVV-2):c.952C>G(p.Gln318Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 22)

Exomes 𝑓: 0.0000019 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ERVV-2
NM_001191055.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.305

Variant links:

Genes affected

ERVV-2 (HGNC:39051): (endogenous retrovirus group V member 2, envelope) Many different human endogenous retrovirus (HERV) families are expressed in normal placental tissue at high levels, suggesting that HERVs are functionally important in reproduction. This gene is part of an HERV provirus on human chromosome 19 that has inactivating mutations in the gag and pol genes. This envelope glycoprotein gene appears to have been selectively preserved. The gene's protein product is expressed in the placenta and acts as a syncytin in Old World monkeys, but has lost the fusogenic activity in humans and other primate lineages. [provided by RefSeq, Jun 2015]

ERVV-2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06589258).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERVV-2	NM_001191055.2 link	c.952C>G	p.Gln318Glu	missense_variant	Exon 2 of 2	ENST00000601417.3	NP_001177984.1	B6SEH9M9QSX5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERVV-2	ENST00000601417.3 link	c.952C>G	p.Gln318Glu	missense_variant	Exon 2 of 2	4	NM_001191055.2	ENSP00000472919.1		B6SEH9

Frequencies

GnomAD3 genomes

AF:

0.00000672

AC:

AN:

148708

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000250

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000193

AC:

AN:

1036860

Hom.:

Cov.:

AF XY:

0.00000191

AC XY:

AN XY:

523574

show subpopulations

Gnomad4 AFR exome

AF:

0.0000421

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000130

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000672

AC:

AN:

148824

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72510

show subpopulations

Gnomad4 AFR

AF:

0.0000249

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:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 06, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.952C>G (p.Q318E) alteration is located in exon 2 (coding exon 1) of the ERVV-2 gene. This alteration results from a C to G substitution at nucleotide position 952, causing the glutamine (Q) at amino acid position 318 to be replaced by a glutamic acid (E). 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

0.14

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.72

CADD

Benign

9.2

DANN

Benign

0.69

DEOGEN2

Benign

0.0017

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.46

M_CAP

Benign

0.024

MetaRNN

Benign

0.066

MutationAssessor

Benign

1.6

PrimateAI

Benign

0.44

Sift4G

Benign

0.099

Vest4

0.099

MVP

0.23

GERP RS

0.42

Varity_R

0.22

gMVP

0.099

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over