19-44860443-A-G

Variant names:

• chr19-44860443-A-G
• rs12978931
• NM_001042724.2:c.89-4828A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001042724.2(NECTIN2):​c.89-4828A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 151,934 control chromosomes in the GnomAD database, including 3,100 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 0.19 (3100 hom., cov: 31)
• Consequence: NECTIN2 NM_001042724.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.756
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.443 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.89-4828A>G		intron	N/A	NP_001036189.1
	NECTIN2	NM_002856.3		c.89-4828A>G		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.89-4828A>G		intron	N/A	ENSP00000252483.4
	NECTIN2	ENST00000252485.8	TSL:1	c.89-4828A>G		intron	N/A	ENSP00000252485.3

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29384 AN: 151816 Hom.: 3092 Cov.: 31

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.194 AC: 29411 AN: 151934 Hom.: 3100 Cov.: 31 AF XY: 0.196 AC XY: 14542 AN XY: 74270

African (AFR) AF: 0.174 AC: 7227 AN: 41440

American (AMR) AF: 0.181 AC: 2752 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 530 AN: 3458

East Asian (EAS) AF: 0.458 AC: 2359 AN: 5150

South Asian (SAS) AF: 0.299 AC: 1438 AN: 4812

European-Finnish (FIN) AF: 0.175 AC: 1848 AN: 10552

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12583 AN: 67962

Other (OTH) AF: 0.207 AC: 438 AN: 2114

Alfa AF: 0.177 Hom.: 314

Bravo AF: 0.197

Asia WGS AF: 0.315 AC: 1093 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.4
DANN	Benign	0.42
PhyloP100		-0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs12978931; hg19: chr19-45363700; COSMIC: COSV52979639;