19-44879804-G-T

Variant names:

• chr19-44879804-G-T
• rs3852861
• NM_001042724.2:c.1043-2407G>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.1043-2407G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 151,924 control chromosomes in the GnomAD database, including 14,243 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 0.42 (14243 hom., cov: 32)
• Consequence: NECTIN2 NM_001042724.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.480
• Publications: 26 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 (EAS) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NECTIN2	NM_001042724.2	c.1043-2407G>T		intron_variant	Intron 5 of 8	ENST00000252483.10	NP_001036189.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NECTIN2	ENST00000252483.10	c.1043-2407G>T		intron_variant	Intron 5 of 8	1	NM_001042724.2	ENSP00000252483.4

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64001 AN: 151806 Hom.: 14253 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.453

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

GnomAD4 genome AF: 0.421 AC: 64008 AN: 151924 Hom.: 14243 Cov.: 32 AF XY: 0.425 AC XY: 31567 AN XY: 74248

African (AFR) AF: 0.333 AC: 13781 AN: 41418

American (AMR) AF: 0.556 AC: 8490 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1610 AN: 3470

East Asian (EAS) AF: 0.755 AC: 3886 AN: 5146

South Asian (SAS) AF: 0.569 AC: 2733 AN: 4804

European-Finnish (FIN) AF: 0.393 AC: 4156 AN: 10570

Middle Eastern (MID) AF: 0.527 AC: 154 AN: 292

European-Non Finnish (NFE) AF: 0.410 AC: 27836 AN: 67938

Other (OTH) AF: 0.450 AC: 948 AN: 2108

Alfa AF: 0.397 Hom.: 2265

Bravo AF: 0.434

Asia WGS AF: 0.602 AC: 2093 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	0.72
DANN	Benign	0.77
PhyloP100		-0.48
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3852861; hg19: chr19-45383061;