chr19-44880326-G-A

Variant names:

• chr19-44880326-G-A
• rs41290122
• NM_001042724.2:c.1043-1885G>A

Variant summary

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

The NM_001042724.2(NECTIN2):​c.1043-1885G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0258 in 152,124 control chromosomes in the GnomAD database, including 105 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 0.026 (105 hom., cov: 31)
• Consequence: NECTIN2 NM_001042724.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.489
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NECTIN2	NM_001042724.2	c.1043-1885G>A		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.1043-1885G>A		intron_variant	Intron 5 of 8	1	NM_001042724.2	ENSP00000252483.4

Frequencies

GnomAD3 genomes AF: 0.0258 AC: 3923 AN: 152006 Hom.: 106 Cov.: 31

Gnomad AFR AF: 0.0234

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0980

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.0179

Gnomad SAS AF: 0.0206

Gnomad FIN AF: 0.0138

Gnomad MID AF: 0.0350

Gnomad NFE AF: 0.0146

Gnomad OTH AF: 0.0340

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

GnomAD4 genome AF: 0.0258 AC: 3924 AN: 152124 Hom.: 105 Cov.: 31 AF XY: 0.0272 AC XY: 2026 AN XY: 74382

African (AFR) AF: 0.0234 AC: 970 AN: 41516

American (AMR) AF: 0.0978 AC: 1490 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.0144 AC: 50 AN: 3468

East Asian (EAS) AF: 0.0180 AC: 93 AN: 5176

South Asian (SAS) AF: 0.0204 AC: 98 AN: 4812

European-Finnish (FIN) AF: 0.0138 AC: 146 AN: 10592

Middle Eastern (MID) AF: 0.0377 AC: 11 AN: 292

European-Non Finnish (NFE) AF: 0.0146 AC: 990 AN: 68002

Other (OTH) AF: 0.0346 AC: 73 AN: 2112

Alfa AF: 0.0168 Hom.: 46

Bravo AF: 0.0319

Asia WGS AF: 0.0400 AC: 138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.42
DANN	Benign	0.79
PhyloP100		-0.49
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: rs41290122; hg19: chr19-45383583;