14-64002788-A-T
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_182914.3(SYNE2):c.3855A>T(p.Val1285=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000038 in 1,605,608 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 0.000028 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000039 ( 0 hom. )
Consequence
SYNE2
NM_182914.3 synonymous
NM_182914.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0240
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=-0.86).
BP6
?
Variant 14-64002788-A-T is Benign according to our data. Variant chr14-64002788-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 538373.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.024 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0000278 (4/143992) while in subpopulation NFE AF= 0.0000464 (3/64604). AF 95% confidence interval is 0.0000123. There are 0 homozygotes in gnomad4. There are 0 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAdExome at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYNE2 | NM_182914.3 | c.3855A>T | p.Val1285= | synonymous_variant | 30/116 | ENST00000555002.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNE2 | ENST00000555002.6 | c.3855A>T | p.Val1285= | synonymous_variant | 30/116 | 1 | NM_182914.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000278 AC: 4AN: 143992Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000201 AC: 5AN: 248968Hom.: 0 AF XY: 0.0000370 AC XY: 5AN XY: 135084
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GnomAD4 exome AF: 0.0000390 AC: 57AN: 1461616Hom.: 0 Cov.: 32 AF XY: 0.0000316 AC XY: 23AN XY: 727068
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | May 06, 2020 | - - |
Emery-Dreifuss muscular dystrophy 5, autosomal dominant Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 10, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at