rs395908

Variant names:

• chr19-44870308-G-A
• rs395908
• NM_001042724.2:c.479-1545G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-44870308-G-A
• chr19-44870308-G-C
• chr19-44870308-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001042724.2(NECTIN2):​c.479-1545G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,030 control chromosomes in the GnomAD database, including 1,982 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 0.16 (1982 hom., cov: 31)
• Consequence: NECTIN2 NM_001042724.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.261
• Publications: 27 publications found

Genes affected

NECTIN2 (HGNC:9707): (nectin cell adhesion molecule 2) This gene encodes a single-pass type I membrane glycoprotein with two Ig-like C2-type domains and an Ig-like V-type domain. This protein is one of the plasma membrane components of adherens junctions. It also serves as an entry for certain mutant strains of herpes simplex virus and pseudorabies virus, and it is involved in cell to cell spreading of these viruses. Variations in this gene have been associated with differences in the severity of multiple sclerosis. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NECTIN2	NM_001042724.2	c.479-1545G>A		intron_variant	Intron 2 of 8	ENST00000252483.10	NP_001036189.1
NECTIN2	NM_002856.3	c.479-1545G>A		intron_variant	Intron 2 of 5		NP_002847.1
NECTIN2	XM_047439169.1	c.479-1545G>A		intron_variant	Intron 2 of 5		XP_047295125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NECTIN2	ENST00000252483.10	c.479-1545G>A		intron_variant	Intron 2 of 8	1	NM_001042724.2	ENSP00000252483.4
NECTIN2	ENST00000252485.8	c.479-1545G>A		intron_variant	Intron 2 of 5	1		ENSP00000252485.3

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23771 AN: 151912 Hom.: 1972 Cov.: 31

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.0622

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.148

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.157 AC: 23823 AN: 152030 Hom.: 1982 Cov.: 31 AF XY: 0.151 AC XY: 11222 AN XY: 74316

African (AFR) AF: 0.187 AC: 7731 AN: 41452

American (AMR) AF: 0.147 AC: 2240 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 449 AN: 3472

East Asian (EAS) AF: 0.165 AC: 850 AN: 5154

South Asian (SAS) AF: 0.205 AC: 986 AN: 4818

European-Finnish (FIN) AF: 0.0622 AC: 659 AN: 10598

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10489 AN: 67960

Other (OTH) AF: 0.154 AC: 324 AN: 2108

Alfa AF: 0.159 Hom.: 5198

Bravo AF: 0.161

Asia WGS AF: 0.226 AC: 784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.12
DANN	Benign	0.38
PhyloP100		-0.26
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs395908; hg19: chr19-45373565;