chr19-44857967-G-A

Variant names:

• chr19-44857967-G-A
• rs440277
• NM_001042724.2:c.89-7304G>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.89-7304G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 152,106 control chromosomes in the GnomAD database, including 6,868 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 0.29 (6868 hom., cov: 32)
• Consequence: NECTIN2 NM_001042724.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.312
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NECTIN2	NM_001042724.2	c.89-7304G>A		intron_variant	Intron 1 of 8	ENST00000252483.10	NP_001036189.1
NECTIN2	NM_002856.3	c.89-7304G>A		intron_variant	Intron 1 of 5		NP_002847.1
NECTIN2	XM_047439169.1	c.89-7304G>A		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.89-7304G>A		intron_variant	Intron 1 of 8	1	NM_001042724.2	ENSP00000252483.4
NECTIN2	ENST00000252485.8	c.89-7304G>A		intron_variant	Intron 1 of 5	1		ENSP00000252485.3

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44349 AN: 151990 Hom.: 6869 Cov.: 32

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.276

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.292 AC: 44367 AN: 152106 Hom.: 6868 Cov.: 32 AF XY: 0.294 AC XY: 21831 AN XY: 74358

African (AFR) AF: 0.244 AC: 10138 AN: 41502

American (AMR) AF: 0.240 AC: 3659 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1055 AN: 3468

East Asian (EAS) AF: 0.118 AC: 611 AN: 5184

South Asian (SAS) AF: 0.177 AC: 856 AN: 4824

European-Finnish (FIN) AF: 0.443 AC: 4680 AN: 10564

Middle Eastern (MID) AF: 0.283 AC: 82 AN: 290

European-Non Finnish (NFE) AF: 0.329 AC: 22350 AN: 67982

Other (OTH) AF: 0.305 AC: 643 AN: 2110

Alfa AF: 0.307 Hom.: 10473

Bravo AF: 0.274

Asia WGS AF: 0.158 AC: 551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.0
DANN	Benign	0.76
PhyloP100		-0.31
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: rs440277; hg19: chr19-45361224;