chr19-44865167-C-T

Variant names:

• chr19-44865167-C-T
• rs394221
• NM_001042724.2:c.89-104C>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.89-104C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 1,265,088 control chromosomes in the GnomAD database, including 185,777 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 (18858 hom., cov: 31)
  • Exomes 𝑓: 0.54 (166919 hom.)
• Consequence: NECTIN2 NM_001042724.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03
• Publications: 9 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=-0.94).
• 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.89-104C>T		intron_variant	Intron 1 of 8	ENST00000252483.10	NP_001036189.1
NECTIN2	NM_002856.3	c.89-104C>T		intron_variant	Intron 1 of 5		NP_002847.1
NECTIN2	XM_047439169.1	c.89-104C>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.89-104C>T		intron_variant	Intron 1 of 8	1	NM_001042724.2	ENSP00000252483.4
NECTIN2	ENST00000252485.8	c.89-104C>T		intron_variant	Intron 1 of 5	1		ENSP00000252485.3

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73199 AN: 151886 Hom.: 18856 Cov.: 31

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.489

GnomAD4 exome AF: 0.543 AC: 604699 AN: 1113084 Hom.: 166919 AF XY: 0.542 AC XY: 298341 AN XY: 550716

African (AFR) AF: 0.293 AC: 7431 AN: 25338

American (AMR) AF: 0.369 AC: 10073 AN: 27274

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 9725 AN: 18296

East Asian (EAS) AF: 0.557 AC: 20736 AN: 37216

South Asian (SAS) AF: 0.460 AC: 28029 AN: 60998

European-Finnish (FIN) AF: 0.692 AC: 33081 AN: 47776

Middle Eastern (MID) AF: 0.433 AC: 1406 AN: 3246

European-Non Finnish (NFE) AF: 0.555 AC: 469292 AN: 845248

Other (OTH) AF: 0.523 AC: 24926 AN: 47692

GnomAD4 genome AF: 0.482 AC: 73216 AN: 152004 Hom.: 18858 Cov.: 31 AF XY: 0.489 AC XY: 36309 AN XY: 74294

African (AFR) AF: 0.304 AC: 12622 AN: 41452

American (AMR) AF: 0.412 AC: 6287 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 1822 AN: 3468

East Asian (EAS) AF: 0.570 AC: 2934 AN: 5148

South Asian (SAS) AF: 0.472 AC: 2274 AN: 4820

European-Finnish (FIN) AF: 0.711 AC: 7529 AN: 10594

Middle Eastern (MID) AF: 0.401 AC: 117 AN: 292

European-Non Finnish (NFE) AF: 0.561 AC: 38082 AN: 67942

Other (OTH) AF: 0.485 AC: 1024 AN: 2112

Alfa AF: 0.527 Hom.: 11099

Bravo AF: 0.453

Asia WGS AF: 0.459 AC: 1597 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.18
DANN	Benign	0.52
PhyloP100		-2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs394221; hg19: chr19-45368424; COSMIC: COSV52975561;