chr14-63853152-G-A
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2
The NM_182914.3(SYNE2):c.-52+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00743 in 151,698 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0074 ( 6 hom., cov: 32)
Exomes 𝑓: 0.0083 ( 0 hom. )
Consequence
SYNE2
NM_182914.3 intron
NM_182914.3 intron
Scores
1
1
Clinical Significance
Conservation
PhyloP100: 1.19
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 -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
?
Variant 14-63853152-G-A is Benign according to our data. Variant chr14-63853152-G-A is described in ClinVar as [Benign]. Clinvar id is 313481.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-63853152-G-A is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00743 (1126/151578) while in subpopulation AMR AF= 0.0169 (258/15232). AF 95% confidence interval is 0.0152. There are 6 homozygotes in gnomad4. There are 541 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 1128 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYNE2 | NM_182914.3 | c.-52+9G>A | intron_variant | ENST00000555002.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNE2 | ENST00000555002.6 | c.-52+9G>A | intron_variant | 1 | NM_182914.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00745 AC: 1128AN: 151470Hom.: 6 Cov.: 32
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GnomAD4 exome AF: 0.00833 AC: 1AN: 120Hom.: 0 Cov.: 0 AF XY: 0.0109 AC XY: 1AN XY: 92
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GnomAD4 genome ? AF: 0.00743 AC: 1126AN: 151578Hom.: 6 Cov.: 32 AF XY: 0.00730 AC XY: 541AN XY: 74086
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Emery-Dreifuss muscular dystrophy 5, autosomal dominant Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
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