rs201176149
Positions:
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_182914.3(SYNE2):āc.1154A>Gā(p.Asn385Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000352 in 1,608,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.00041 ( 0 hom., cov: 28)
Exomes š: 0.00035 ( 0 hom. )
Consequence
SYNE2
NM_182914.3 missense
NM_182914.3 missense
Scores
5
13
Clinical Significance
Conservation
PhyloP100: 6.06
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.009871334).
BP6
?
Variant 14-63976588-A-G is Benign according to our data. Variant chr14-63976588-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 283981.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=3, Likely_benign=1, Benign=1}. Variant chr14-63976588-A-G is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000413 (61/147598) while in subpopulation AMR AF= 0.000612 (9/14696). AF 95% confidence interval is 0.000319. There are 0 homozygotes in gnomad4. There are 29 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 61 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYNE2 | NM_182914.3 | c.1154A>G | p.Asn385Ser | missense_variant | 12/116 | ENST00000555002.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNE2 | ENST00000555002.6 | c.1154A>G | p.Asn385Ser | missense_variant | 12/116 | 1 | NM_182914.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000407 AC: 60AN: 147516Hom.: 0 Cov.: 28
GnomAD3 genomes
?
AF:
AC:
60
AN:
147516
Hom.:
Cov.:
28
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000334 AC: 83AN: 248570Hom.: 0 AF XY: 0.000341 AC XY: 46AN XY: 134906
GnomAD3 exomes
AF:
AC:
83
AN:
248570
Hom.:
AF XY:
AC XY:
46
AN XY:
134906
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000346 AC: 505AN: 1460670Hom.: 0 Cov.: 37 AF XY: 0.000322 AC XY: 234AN XY: 726630
GnomAD4 exome
AF:
AC:
505
AN:
1460670
Hom.:
Cov.:
37
AF XY:
AC XY:
234
AN XY:
726630
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000413 AC: 61AN: 147598Hom.: 0 Cov.: 28 AF XY: 0.000404 AC XY: 29AN XY: 71788
GnomAD4 genome
?
AF:
AC:
61
AN:
147598
Hom.:
Cov.:
28
AF XY:
AC XY:
29
AN XY:
71788
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
4
ExAC
?
AF:
AC:
29
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:3Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Emery-Dreifuss muscular dystrophy 5, autosomal dominant Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 14, 2019 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 02, 2021 | The c.1154A>G (p.N385S) alteration is located in exon 12 (coding exon 11) of the SYNE2 gene. This alteration results from a A to G substitution at nucleotide position 1154, causing the asparagine (N) at amino acid position 385 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 13, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;M;.
MutationTaster
Benign
D;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;.;N;N
REVEL
Benign
Sift
Uncertain
D;.;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
B;.;B;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at