6-132752672-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004665.6(VNN2):c.615G>T(p.Arg205Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00709 in 1,614,104 control chromosomes in the GnomAD database, including 77 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0074 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0071 (68 hom.)
• Consequence: VNN2 NM_004665.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.846

Genes affected

VNN2 (HGNC:12706): (vanin 2) This gene product is a member of the Vanin family of proteins that share extensive sequence similarity with each other, and also with biotinidase. The family includes secreted and membrane-associated proteins, a few of which have been reported to participate in hematopoietic cell trafficking. No biotinidase activity has been demonstrated for any of the vanin proteins, however, they possess pantetheinase activity, which may play a role in oxidative-stress response. The encoded protein is a GPI-anchored cell surface molecule that plays a role in transendothelial migration of neutrophils. This gene lies in close proximity to, and in same transcriptional orientation as two other vanin genes on chromosome 6q23-q24. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, May 2011]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00540179).
• BP6: Variant 6-132752672-C-A is Benign according to our data. Variant chr6-132752672-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2656918.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00706 (10323/1461862) while in subpopulation MID AF= 0.0191 (110/5768). AF 95% confidence interval is 0.0162. There are 68 homozygotes in gnomad4_exome. There are 5161 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VNN2	NM_004665.6	c.615G>T	p.Arg205Ser	missense_variant	4/7	ENST00000326499.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VNN2	ENST00000326499.11	c.615G>T	p.Arg205Ser	missense_variant	4/7	1	NM_004665.6	P1
	ENST00000430895.1			upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.00738 AC: 1122 AN: 152124 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00123

Gnomad AMI AF: 0.0681

Gnomad AMR AF: 0.00615

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00683

Gnomad FIN AF: 0.00981

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.0110

Gnomad OTH AF: 0.00718

GnomAD3 exomes AF: 0.00660 AC: 1659 AN: 251400 Hom.: 13 AF XY: 0.00679 AC XY: 922 AN XY: 135862

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.00335

Gnomad ASJ exome AF: 0.00149

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00565

Gnomad FIN exome AF: 0.0113

Gnomad NFE exome AF: 0.00918

Gnomad OTH exome AF: 0.00750

GnomAD4 exome AF: 0.00706 AC: 10323 AN: 1461862 Hom.: 68 Cov.: 30 AF XY: 0.00710 AC XY: 5161 AN XY: 727232

Gnomad4 AFR exome AF: 0.000986

Gnomad4 AMR exome AF: 0.00342

Gnomad4 ASJ exome AF: 0.00142

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00559

Gnomad4 FIN exome AF: 0.0114

Gnomad4 NFE exome AF: 0.00765

Gnomad4 OTH exome AF: 0.00652

GnomAD4 genome AF: 0.00737 AC: 1122 AN: 152242 Hom.: 9 Cov.: 32 AF XY: 0.00752 AC XY: 560 AN XY: 74456

Gnomad4 AFR AF: 0.00123

Gnomad4 AMR AF: 0.00614

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00684

Gnomad4 FIN AF: 0.00981

Gnomad4 NFE AF: 0.0110

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00873 Hom.: 15

Bravo AF: 0.00622

TwinsUK AF: 0.00593 AC: 22

ALSPAC AF: 0.00649 AC: 25

ESP6500AA AF: 0.00159 AC: 7

ESP6500EA AF: 0.0102 AC: 88

ExAC AF: 0.00687 AC: 834

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.00982

EpiControl AF: 0.00954

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

VNN2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.33
Cadd	Benign	16
Dann	Benign	0.81
DEOGEN2	Benign	0.052	T;.
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.30	T;T
MetaRNN	Benign	0.0054	T;T
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.1	M;.
MutationTaster	Benign	0.89	D;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.17
Sift	Benign	0.094	T;T
Sift4G	Uncertain	0.047	D;T
Polyphen		0.0060	B;.
Vest4		0.20
MutPred		0.66		Gain of glycosylation at R205 (P = 0.0662);.;
MVP		0.32
MPC		0.025
ClinPred		0.013	T
GERP RS		1.6
Varity_R		0.13
gMVP		0.51

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: rs34492437; hg19: chr6-133073811; COSMIC: COSV105222780; COSMIC: COSV105222780;