rs374980509
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_182914.3(SYNE2):c.3990G>A(p.Ala1330=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000116 in 1,614,140 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00061 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000064 ( 0 hom. )
Consequence
SYNE2
NM_182914.3 synonymous
NM_182914.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.36
Genes affected
SYNE2 (HGNC:17084): (spectrin repeat containing nuclear envelope protein 2) The protein encoded by this gene is a nuclear outer membrane protein that binds cytoplasmic F-actin. This binding tethers the nucleus to the cytoskeleton and aids in the maintenance of the structural integrity of the nucleus. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 14-64002923-G-A is Benign according to our data. Variant chr14-64002923-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 538358.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.36 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000611 (93/152270) while in subpopulation AFR AF= 0.00183 (76/41554). AF 95% confidence interval is 0.0015. There are 1 homozygotes in gnomad4. There are 42 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 93 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYNE2 | NM_182914.3 | c.3990G>A | p.Ala1330= | synonymous_variant | 30/116 | ENST00000555002.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNE2 | ENST00000555002.6 | c.3990G>A | p.Ala1330= | synonymous_variant | 30/116 | 1 | NM_182914.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000618 AC: 94AN: 152152Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000169 AC: 42AN: 249154Hom.: 0 AF XY: 0.000111 AC XY: 15AN XY: 135160
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GnomAD4 exome AF: 0.0000643 AC: 94AN: 1461870Hom.: 0 Cov.: 32 AF XY: 0.0000468 AC XY: 34AN XY: 727230
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GnomAD4 genome AF: 0.000611 AC: 93AN: 152270Hom.: 1 Cov.: 32 AF XY: 0.000564 AC XY: 42AN XY: 74442
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2023 | SYNE2: BP4, BP7 - |
SYNE2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 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). - |
Emery-Dreifuss muscular dystrophy 5, autosomal dominant Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 20, 2023 | - - |
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