chr19-44865309-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001042724.2(NECTIN2):​c.127C>T​(p.Arg43Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NECTIN2
NM_001042724.2 stop_gained

Scores

2
2
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.09
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NECTIN2NM_001042724.2 linkuse as main transcriptc.127C>T p.Arg43Ter stop_gained 2/9 ENST00000252483.10
NECTIN2NM_002856.3 linkuse as main transcriptc.127C>T p.Arg43Ter stop_gained 2/6
NECTIN2XM_047439169.1 linkuse as main transcriptc.127C>T p.Arg43Ter stop_gained 2/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NECTIN2ENST00000252483.10 linkuse as main transcriptc.127C>T p.Arg43Ter stop_gained 2/91 NM_001042724.2 P3Q92692-1
NECTIN2ENST00000252485.8 linkuse as main transcriptc.127C>T p.Arg43Ter stop_gained 2/61 A2Q92692-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461342
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
726950
show subpopulations
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Cerebral palsy Uncertain:1
Uncertain significance, criteria provided, single submitterresearchNeurogenetics Research Program, University of AdelaideJun 10, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.37
D
BayesDel_noAF
Pathogenic
0.29
CADD
Pathogenic
36
DANN
Uncertain
1.0
Eigen
Uncertain
0.38
Eigen_PC
Benign
0.080
FATHMM_MKL
Benign
0.15
N
MutationTaster
Benign
1.0
A;A
Vest4
0.60
GERP RS
4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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: chr19-45368566; API