19-44865261-C-T
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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
NM_001042724.2 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.0004510
2
Clinical Significance
Conservation
PhyloP100: 1.40
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]
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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 |
---|---|---|---|---|---|---|---|
NECTIN2 | NM_001042724.2 | c.89-10C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000252483.10 | |||
NECTIN2 | NM_002856.3 | c.89-10C>T | splice_polypyrimidine_tract_variant, intron_variant | ||||
NECTIN2 | XM_047439169.1 | c.89-10C>T | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NECTIN2 | ENST00000252483.10 | c.89-10C>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001042724.2 | P3 | |||
NECTIN2 | ENST00000252485.8 | c.89-10C>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | A2 |
Frequencies
GnomAD3 genomes AF: 0.00129 AC: 196AN: 152122Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000313 AC: 76AN: 242830Hom.: 0 AF XY: 0.000183 AC XY: 24AN XY: 131234
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GnomAD4 exome AF: 0.000102 AC: 148AN: 1449516Hom.: 0 Cov.: 32 AF XY: 0.0000876 AC XY: 63AN XY: 719358
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GnomAD4 genome AF: 0.00129 AC: 196AN: 152240Hom.: 0 Cov.: 31 AF XY: 0.00117 AC XY: 87AN XY: 74446
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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 provided | clinical testing | PreventionGenetics, part of Exact Sciences | May 06, 2022 | This 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
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at