chr19-44848680-T-C

Variant names:

• chr19-44848680-T-C
• rs1871046
• NM_001042724.2:c.88+2067T>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.88+2067T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 148,636 control chromosomes in the GnomAD database, including 8,375 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 (8375 hom., cov: 25)
• Consequence: NECTIN2 NM_001042724.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.506
• Publications: 11 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042724.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NECTIN2	NM_001042724.2	MANE Select	c.88+2067T>C		intron	N/A	NP_001036189.1	Q92692-1
	NECTIN2	NM_002856.3		c.88+2067T>C		intron	N/A	NP_002847.1	Q92692-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NECTIN2	ENST00000252483.10	TSL:1 MANE Select	c.88+2067T>C		intron	N/A	ENSP00000252483.4	Q92692-1
	NECTIN2	ENST00000252485.8	TSL:1	c.88+2067T>C		intron	N/A	ENSP00000252485.3	Q92692-2
	NECTIN2	ENST00000883539.1		c.88+2067T>C		intron	N/A	ENSP00000553598.1

Frequencies

GnomAD3 genomes AF: 0.317 AC: 47108 AN: 148526 Hom.: 8370 Cov.: 25

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.317 AC: 47130 AN: 148636 Hom.: 8375 Cov.: 25 AF XY: 0.318 AC XY: 23021 AN XY: 72336

African (AFR) AF: 0.147 AC: 5890 AN: 40076

American (AMR) AF: 0.374 AC: 5584 AN: 14912

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1211 AN: 3444

East Asian (EAS) AF: 0.196 AC: 985 AN: 5022

South Asian (SAS) AF: 0.404 AC: 1884 AN: 4666

European-Finnish (FIN) AF: 0.399 AC: 3990 AN: 9996

Middle Eastern (MID) AF: 0.303 AC: 88 AN: 290

European-Non Finnish (NFE) AF: 0.394 AC: 26490 AN: 67270

Other (OTH) AF: 0.329 AC: 677 AN: 2056

Alfa AF: 0.340 Hom.: 1179

Bravo AF: 0.300

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.0
DANN	Benign	0.60
PhyloP100		-0.51
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1871046;

hg19: chr19-45351937;