chr19-44865063-C-T

Variant names:

• chr19-44865063-C-T
• rs419010
• NM_001042724.2:c.89-208C>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.89-208C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 152,036 control chromosomes in the GnomAD database, including 18,868 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 0.48 (18868 hom., cov: 31)
• Consequence: NECTIN2 NM_001042724.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.708
• Publications: 10 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=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NECTIN2	NM_001042724.2	c.89-208C>T		intron_variant	Intron 1 of 8	ENST00000252483.10	NP_001036189.1
NECTIN2	NM_002856.3	c.89-208C>T		intron_variant	Intron 1 of 5		NP_002847.1
NECTIN2	XM_047439169.1	c.89-208C>T		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.89-208C>T		intron_variant	Intron 1 of 8	1	NM_001042724.2	ENSP00000252483.4
NECTIN2	ENST00000252485.8	c.89-208C>T		intron_variant	Intron 1 of 5	1		ENSP00000252485.3

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73247 AN: 151918 Hom.: 18866 Cov.: 31

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.397

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.482 AC: 73265 AN: 152036 Hom.: 18868 Cov.: 31 AF XY: 0.489 AC XY: 36351 AN XY: 74342

African (AFR) AF: 0.305 AC: 12633 AN: 41450

American (AMR) AF: 0.413 AC: 6307 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 1821 AN: 3466

East Asian (EAS) AF: 0.570 AC: 2942 AN: 5164

South Asian (SAS) AF: 0.473 AC: 2280 AN: 4822

European-Finnish (FIN) AF: 0.711 AC: 7528 AN: 10590

Middle Eastern (MID) AF: 0.407 AC: 118 AN: 290

European-Non Finnish (NFE) AF: 0.560 AC: 38085 AN: 67956

Other (OTH) AF: 0.485 AC: 1026 AN: 2114

Alfa AF: 0.504 Hom.: 5176

Bravo AF: 0.453

Asia WGS AF: 0.460 AC: 1599 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.22
PhyloP100		-0.71
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: rs419010; hg19: chr19-45368320;