19-44865167-C-G

Variant names:

• chr19-44865167-C-G
• rs394221
• NM_001042724.2:c.89-104C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001042724.2(NECTIN2):​c.89-104C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000179 in 1,115,710 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: NECTIN2 NM_001042724.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

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.89-104C>G		intron	N/A	NP_001036189.1	Q92692-1
	NECTIN2	NM_002856.3		c.89-104C>G		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.89-104C>G		intron	N/A	ENSP00000252483.4	Q92692-1
	NECTIN2	ENST00000252485.8	TSL:1	c.89-104C>G		intron	N/A	ENSP00000252485.3	Q92692-2
	NECTIN2	ENST00000883539.1		c.230-104C>G		intron	N/A	ENSP00000553598.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000179 AC: 2 AN: 1115710 Hom.: 0 AF XY: 0.00000181 AC XY: 1 AN XY: 551944

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25368

American (AMR) AF: 0.00 AC: 0 AN: 27316

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18316

East Asian (EAS) AF: 0.00 AC: 0 AN: 37246

South Asian (SAS) AF: 0.00 AC: 0 AN: 61138

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47818

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3254

European-Non Finnish (NFE) AF: 0.00000236 AC: 2 AN: 847468

Other (OTH) AF: 0.00 AC: 0 AN: 47786

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.11
DANN	Benign	0.36
PhyloP100		-2.0

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;