rs2075642

Variant names:

• chr19-44874210-G-A
• rs2075642
• NM_001042724.2:c.894-120G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-44874210-G-A
• chr19-44874210-G-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.894-120G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,351,646 control chromosomes in the GnomAD database, including 27,487 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 0.20 (3024 hom., cov: 31)
  • Exomes 𝑓: 0.20 (24463 hom.)
• Consequence: NECTIN2 NM_001042724.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.325
• Publications: 27 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=-0.76).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.241 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NECTIN2	NM_001042724.2	MANE Select	c.894-120G>A		intron	N/A	NP_001036189.1
	NECTIN2	NM_002856.3		c.894-120G>A		intron	N/A	NP_002847.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NECTIN2	ENST00000252483.10	TSL:1 MANE Select	c.894-120G>A		intron	N/A	ENSP00000252483.4
	NECTIN2	ENST00000252485.8	TSL:1	c.894-120G>A		intron	N/A	ENSP00000252485.3
	NECTIN2	ENST00000591581.1	TSL:2	c.414-120G>A		intron	N/A	ENSP00000465587.1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29963 AN: 151882 Hom.: 3026 Cov.: 31

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.207

GnomAD4 exome AF: 0.199 AC: 238957 AN: 1199646 Hom.: 24463 Cov.: 18 AF XY: 0.200 AC XY: 119852 AN XY: 599126

African (AFR) AF: 0.169 AC: 4610 AN: 27206

American (AMR) AF: 0.297 AC: 10243 AN: 34448

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 4726 AN: 20362

East Asian (EAS) AF: 0.180 AC: 6872 AN: 38106

South Asian (SAS) AF: 0.215 AC: 15533 AN: 72354

European-Finnish (FIN) AF: 0.167 AC: 7892 AN: 47376

Middle Eastern (MID) AF: 0.295 AC: 1149 AN: 3894

European-Non Finnish (NFE) AF: 0.196 AC: 177387 AN: 904928

Other (OTH) AF: 0.207 AC: 10545 AN: 50972

GnomAD4 genome AF: 0.197 AC: 29967 AN: 152000 Hom.: 3024 Cov.: 31 AF XY: 0.197 AC XY: 14630 AN XY: 74274

African (AFR) AF: 0.176 AC: 7316 AN: 41462

American (AMR) AF: 0.247 AC: 3773 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 776 AN: 3466

East Asian (EAS) AF: 0.204 AC: 1051 AN: 5146

South Asian (SAS) AF: 0.214 AC: 1031 AN: 4816

European-Finnish (FIN) AF: 0.158 AC: 1675 AN: 10594

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13547 AN: 67940

Other (OTH) AF: 0.205 AC: 432 AN: 2104

Alfa AF: 0.201 Hom.: 7349

Bravo AF: 0.207

Asia WGS AF: 0.206 AC: 716 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.9
DANN	Benign	0.63
PhyloP100		-0.33
PromoterAI		-0.015	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2075642; hg19: chr19-45377467; COSMIC: COSV107256514; COSMIC: COSV107256514;