rs2083905904

Variant names:

• chr19-53050045-T-G
• rs2083905904
• NM_001191055.2:c.794T>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001191055.2(ERVV-2):​c.794T>G​(p.Leu265Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000045 in 1,333,378 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 0.0000045 (0 hom.)
• Consequence: ERVV-2 NM_001191055.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.308

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18734607).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERVV-2	NM_001191055.2	c.794T>G	p.Leu265Arg	missense_variant	Exon 2 of 2	ENST00000601417.3	NP_001177984.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERVV-2	ENST00000601417.3	c.794T>G	p.Leu265Arg	missense_variant	Exon 2 of 2	4	NM_001191055.2	ENSP00000472919.1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome AF: 0.00000450 AC: 6 AN: 1333378 Hom.: 0 Cov.: 32 AF XY: 0.00000456 AC XY: 3 AN XY: 658586

Gnomad4 AFR exome AF: 0.0000668

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: 9.64e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 20

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 23, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.794T>G (p.L265R) alteration is located in exon 2 (coding exon 1) of the ERVV-2 gene. This alteration results from a T to G substitution at nucleotide position 794, causing the leucine (L) at amino acid position 265 to be replaced by an arginine (R). 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	Pathogenic	0.85
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Benign	0.71
DEOGEN2	Benign	0.0052	T
FATHMM_MKL	Benign	0.0036	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.19	T
MutationAssessor	Benign	1.7	L
PrimateAI	Benign	0.42	T
Sift4G	Pathogenic	0.0	D
Vest4		0.33
MVP		0.42
GERP RS		0.42
Varity_R		0.20
gMVP		0.54

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: rs2083905904; hg19: chr19-53553298;