chr14-64225135-C-T
Variant names:
Variant summary
Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_182914.3(SYNE2):c.20516+90C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0737 in 1,564,992 control chromosomes in the GnomAD database, including 4,934 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.056 ( 327 hom., cov: 32)
Exomes 𝑓: 0.076 ( 4607 hom. )
Consequence
SYNE2
NM_182914.3 intron
NM_182914.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.435
Publications
9 publications found
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]
ESR2 (HGNC:3468): (estrogen receptor 2) This gene encodes a member of the family of estrogen receptors and superfamily of nuclear receptor transcription factors. The gene product contains an N-terminal DNA binding domain and C-terminal ligand binding domain and is localized to the nucleus, cytoplasm, and mitochondria. Upon binding to 17beta-estradiol or related ligands, the encoded protein forms homo- or hetero-dimers that interact with specific DNA sequences to activate transcription. Some isoforms dominantly inhibit the activity of other estrogen receptor family members. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been fully characterized. [provided by RefSeq, Jul 2008]
ESR2 Gene-Disease associations (from GenCC):
- male infertility with azoospermia or oligozoospermia due to single gene mutationInheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center
- familial medullary thyroid carcinomaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- ovarian dysgenesis 8Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
Variant 14-64225135-C-T is Benign according to our data. Variant chr14-64225135-C-T is described in ClinVar as [Benign]. Clinvar id is 1295983.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0778 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SYNE2 | NM_182914.3 | c.20516+90C>T | intron_variant | Intron 115 of 115 | ENST00000555002.6 | NP_878918.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SYNE2 | ENST00000555002.6 | c.20516+90C>T | intron_variant | Intron 115 of 115 | 1 | NM_182914.3 | ENSP00000450831.2 |
Frequencies
GnomAD3 genomes AF: 0.0559 AC: 8502AN: 152004Hom.: 326 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
8502
AN:
152004
Hom.:
Cov.:
32
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:
GnomAD4 exome AF: 0.0757 AC: 106903AN: 1412870Hom.: 4607 Cov.: 24 AF XY: 0.0743 AC XY: 52247AN XY: 703602 show subpopulations
GnomAD4 exome
AF:
AC:
106903
AN:
1412870
Hom.:
Cov.:
24
AF XY:
AC XY:
52247
AN XY:
703602
show subpopulations
African (AFR)
AF:
AC:
415
AN:
32434
American (AMR)
AF:
AC:
3688
AN:
41988
Ashkenazi Jewish (ASJ)
AF:
AC:
1501
AN:
25518
East Asian (EAS)
AF:
AC:
315
AN:
39230
South Asian (SAS)
AF:
AC:
2451
AN:
83856
European-Finnish (FIN)
AF:
AC:
4791
AN:
52812
Middle Eastern (MID)
AF:
AC:
82
AN:
5674
European-Non Finnish (NFE)
AF:
AC:
89955
AN:
1072630
Other (OTH)
AF:
AC:
3705
AN:
58728
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
5255
10510
15766
21021
26276
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Exome Hom
Variant carriers
0
3278
6556
9834
13112
16390
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome AF: 0.0559 AC: 8509AN: 152122Hom.: 327 Cov.: 32 AF XY: 0.0552 AC XY: 4101AN XY: 74360 show subpopulations
GnomAD4 genome
AF:
AC:
8509
AN:
152122
Hom.:
Cov.:
32
AF XY:
AC XY:
4101
AN XY:
74360
show subpopulations
African (AFR)
AF:
AC:
623
AN:
41526
American (AMR)
AF:
AC:
915
AN:
15290
Ashkenazi Jewish (ASJ)
AF:
AC:
204
AN:
3468
East Asian (EAS)
AF:
AC:
49
AN:
5178
South Asian (SAS)
AF:
AC:
121
AN:
4814
European-Finnish (FIN)
AF:
AC:
982
AN:
10576
Middle Eastern (MID)
AF:
AC:
2
AN:
294
European-Non Finnish (NFE)
AF:
AC:
5410
AN:
67954
Other (OTH)
AF:
AC:
112
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
393
786
1178
1571
1964
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Genome Hom
Variant carriers
0
96
192
288
384
480
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
82
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Jul 09, 2018
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
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
Publications
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