rs2083905904

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-53050045-T-C
• chr19-53050045-T-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>C​(p.Leu265Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000075 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: ERVV-2 NM_001191055.2 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.22464007).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERVV-2	NM_001191055.2	c.794T>C	p.Leu265Pro	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>C	p.Leu265Pro	missense_variant	Exon 2 of 2	4	NM_001191055.2	ENSP00000472919.1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome AF: 7.50e-7 AC: 1 AN: 1333378 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 658586

Gnomad4 AFR exome AF: 0.00

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	18
DANN	Benign	0.70
DEOGEN2	Benign	0.0047	T
FATHMM_MKL	Benign	0.0030	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.22	T
MutationAssessor	Benign	1.7	L
PrimateAI	Benign	0.43	T
Sift4G	Pathogenic	0.0	D
Vest4		0.38
MVP		0.50
GERP RS		0.42
Varity_R		0.29
gMVP		0.58

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-53553298;