chr19-44848489-A-G

Variant names:

• chr19-44848489-A-G
• rs1871047
• NM_001042724.2:c.88+1876A>G

Variant summary

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

The NM_001042724.2(NECTIN2):​c.88+1876A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 151,828 control chromosomes in the GnomAD database, including 8,559 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 0.32 (8559 hom., cov: 31)
• Consequence: NECTIN2 NM_001042724.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.642
• Publications: 28 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 = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NECTIN2	NM_001042724.2	c.88+1876A>G		intron_variant	Intron 1 of 8	ENST00000252483.10	NP_001036189.1
NECTIN2	NM_002856.3	c.88+1876A>G		intron_variant	Intron 1 of 5		NP_002847.1
NECTIN2	XM_047439169.1	c.88+1876A>G		intron_variant	Intron 1 of 5		XP_047295125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NECTIN2	ENST00000252483.10	c.88+1876A>G		intron_variant	Intron 1 of 8	1	NM_001042724.2	ENSP00000252483.4
NECTIN2	ENST00000252485.8	c.88+1876A>G		intron_variant	Intron 1 of 5	1		ENSP00000252485.3

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47919 AN: 151710 Hom.: 8554 Cov.: 31

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.316 AC: 47941 AN: 151828 Hom.: 8559 Cov.: 31 AF XY: 0.318 AC XY: 23591 AN XY: 74186

African (AFR) AF: 0.146 AC: 6048 AN: 41450

American (AMR) AF: 0.374 AC: 5700 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1214 AN: 3468

East Asian (EAS) AF: 0.195 AC: 997 AN: 5108

South Asian (SAS) AF: 0.405 AC: 1943 AN: 4800

European-Finnish (FIN) AF: 0.401 AC: 4228 AN: 10548

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.393 AC: 26701 AN: 67894

Other (OTH) AF: 0.327 AC: 689 AN: 2106

Alfa AF: 0.362 Hom.: 33296

Bravo AF: 0.300

Asia WGS AF: 0.288 AC: 1004 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	3.4
DANN	Benign	0.72
PhyloP100		-0.64
Mutation Taster		=8/92	disease causing

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: rs1871047; hg19: chr19-45351746;