chr19-44873962-C-T
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_001042724.2(NECTIN2):c.822C>T(p.Leu274=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000353 in 1,613,988 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 (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000036 ( 0 hom. )
Consequence
NECTIN2
NM_001042724.2 synonymous
NM_001042724.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.25
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 -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
Variant 19-44873962-C-T is Benign according to our data. Variant chr19-44873962-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2650088.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-3.25 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NECTIN2 | NM_001042724.2 | c.822C>T | p.Leu274= | synonymous_variant | 4/9 | ENST00000252483.10 | |
NECTIN2 | NM_002856.3 | c.822C>T | p.Leu274= | synonymous_variant | 4/6 | ||
NECTIN2 | XM_047439169.1 | c.822C>T | p.Leu274= | synonymous_variant | 4/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NECTIN2 | ENST00000252483.10 | c.822C>T | p.Leu274= | synonymous_variant | 4/9 | 1 | NM_001042724.2 | P3 | |
NECTIN2 | ENST00000252485.8 | c.822C>T | p.Leu274= | synonymous_variant | 4/6 | 1 | A2 | ||
NECTIN2 | ENST00000591581.1 | c.345C>T | p.Leu115= | synonymous_variant | 2/4 | 2 | |||
NECTIN2 | ENST00000587386.1 | n.21C>T | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152152Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251388Hom.: 0 AF XY: 0.0000736 AC XY: 10AN XY: 135868
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GnomAD4 exome AF: 0.0000363 AC: 53AN: 1461836Hom.: 0 Cov.: 31 AF XY: 0.0000426 AC XY: 31AN XY: 727216
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74328
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
NECTIN2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 21, 2019 | 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). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2023 | NECTIN2: BP4, BP7 - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at