19-44865261-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_001042724.2(NECTIN2):​c.89-10C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000215 in 1,601,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

NECTIN2
NM_001042724.2 splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.0004510
2

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.40
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 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=-0.59).
BP6
Variant 19-44865261-C-T is Benign according to our data. Variant chr19-44865261-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3054519.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NECTIN2NM_001042724.2 linkuse as main transcriptc.89-10C>T splice_polypyrimidine_tract_variant, intron_variant ENST00000252483.10
NECTIN2NM_002856.3 linkuse as main transcriptc.89-10C>T splice_polypyrimidine_tract_variant, intron_variant
NECTIN2XM_047439169.1 linkuse as main transcriptc.89-10C>T splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NECTIN2ENST00000252483.10 linkuse as main transcriptc.89-10C>T splice_polypyrimidine_tract_variant, intron_variant 1 NM_001042724.2 P3Q92692-1
NECTIN2ENST00000252485.8 linkuse as main transcriptc.89-10C>T splice_polypyrimidine_tract_variant, intron_variant 1 A2Q92692-2

Frequencies

GnomAD3 genomes
AF:
0.00129
AC:
196
AN:
152122
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00461
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00144
GnomAD3 exomes
AF:
0.000313
AC:
76
AN:
242830
Hom.:
0
AF XY:
0.000183
AC XY:
24
AN XY:
131234
show subpopulations
Gnomad AFR exome
AF:
0.00446
Gnomad AMR exome
AF:
0.0000586
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000335
GnomAD4 exome
AF:
0.000102
AC:
148
AN:
1449516
Hom.:
0
Cov.:
32
AF XY:
0.0000876
AC XY:
63
AN XY:
719358
show subpopulations
Gnomad4 AFR exome
AF:
0.00408
Gnomad4 AMR exome
AF:
0.0000678
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:
0.00
Gnomad4 OTH exome
AF:
0.000150
GnomAD4 genome
AF:
0.00129
AC:
196
AN:
152240
Hom.:
0
Cov.:
31
AF XY:
0.00117
AC XY:
87
AN XY:
74446
show subpopulations
Gnomad4 AFR
AF:
0.00459
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000964
Hom.:
0
Bravo
AF:
0.00156

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

NECTIN2-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesMay 06, 2022This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.59
CADD
Benign
13
DANN
Benign
0.85

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00045
dbscSNV1_RF
Benign
0.036
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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs376208680; hg19: chr19-45368518; API