19-44865554-G-T

Variant names:

• chr19-44865554-G-T
• NM_001042724.2:c.372G>T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001042724.2(NECTIN2):​c.372G>T​(p.Thr124Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,412,802 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: 0.0000014 (0 hom.)
• Consequence: NECTIN2 NM_001042724.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167

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

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=-0.167 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NECTIN2	NM_001042724.2	c.372G>T	p.Thr124Thr	synonymous_variant	Exon 2 of 9	ENST00000252483.10	NP_001036189.1
NECTIN2	NM_002856.3	c.372G>T	p.Thr124Thr	synonymous_variant	Exon 2 of 6		NP_002847.1
NECTIN2	XM_047439169.1	c.372G>T	p.Thr124Thr	synonymous_variant	Exon 2 of 6		XP_047295125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NECTIN2	ENST00000252483.10	c.372G>T	p.Thr124Thr	synonymous_variant	Exon 2 of 9	1	NM_001042724.2	ENSP00000252483.4
NECTIN2	ENST00000252485.8	c.372G>T	p.Thr124Thr	synonymous_variant	Exon 2 of 6	1		ENSP00000252485.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000142 AC: 2 AN: 1412802 Hom.: 0 Cov.: 32 AF XY: 0.00000143 AC XY: 1 AN XY: 699162

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000123

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000170

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.60
DANN	Benign	0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-45368811; COSMIC: COSV52978261;