rs78754926

Variant names:

• chr19-44881845-G-A
• rs78754926
• NM_001042724.2:c.1043-366G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-44881845-G-A
• chr19-44881845-G-C

Variant summary

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

The NM_001042724.2(NECTIN2):​c.1043-366G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0421 in 152,128 control chromosomes in the GnomAD database, including 252 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 0.042 (252 hom., cov: 31)
• Consequence: NECTIN2 NM_001042724.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.184
• Publications: 4 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]

ENSG00000267282 (HGNC:56209):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NECTIN2	NM_001042724.2	c.1043-366G>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.1043-366G>A		intron_variant	Intron 5 of 8	1	NM_001042724.2	ENSP00000252483.4
ENSG00000267282	ENST00000585408.2	n.*140C>T		downstream_gene_variant		3
ENSG00000267282	ENST00000787383.1	n.*135C>T		downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0420 AC: 6381 AN: 152010 Hom.: 252 Cov.: 31

Gnomad AFR AF: 0.0756

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0288

Gnomad EAS AF: 0.0158

Gnomad SAS AF: 0.0239

Gnomad FIN AF: 0.0137

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0153

Gnomad OTH AF: 0.0546

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

GnomAD4 genome AF: 0.0421 AC: 6399 AN: 152128 Hom.: 252 Cov.: 31 AF XY: 0.0430 AC XY: 3198 AN XY: 74372

African (AFR) AF: 0.0759 AC: 3148 AN: 41498

American (AMR) AF: 0.107 AC: 1637 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0288 AC: 100 AN: 3468

East Asian (EAS) AF: 0.0159 AC: 82 AN: 5168

South Asian (SAS) AF: 0.0235 AC: 113 AN: 4814

European-Finnish (FIN) AF: 0.0137 AC: 145 AN: 10588

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0153 AC: 1038 AN: 67988

Other (OTH) AF: 0.0550 AC: 116 AN: 2110

Alfa AF: 0.0193 Hom.: 103

Bravo AF: 0.0512

Asia WGS AF: 0.0420 AC: 147 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.1
DANN	Benign	0.81
PhyloP100		0.18
PromoterAI		0.010	Neutral
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: rs78754926; hg19: chr19-45385102;