chr14-64225135-C-T

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

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.435

Publications

9 publications found
Variant links:
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 mutation
    Inheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center
  • familial medullary thyroid carcinoma
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • ovarian dysgenesis 8
    Inheritance: 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
SYNE2NM_182914.3 linkc.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
SYNE2ENST00000555002.6 linkc.20516+90C>T intron_variant Intron 115 of 115 1 NM_182914.3 ENSP00000450831.2 Q8WXH0-2A0A0C4DGK3

Frequencies

GnomAD3 genomes
AF:
0.0559
AC:
8502
AN:
152004
Hom.:
326
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0150
Gnomad AMI
AF:
0.100
Gnomad AMR
AF:
0.0596
Gnomad ASJ
AF:
0.0588
Gnomad EAS
AF:
0.00906
Gnomad SAS
AF:
0.0251
Gnomad FIN
AF:
0.0929
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.0796
Gnomad OTH
AF:
0.0536
GnomAD4 exome
AF:
0.0757
AC:
106903
AN:
1412870
Hom.:
4607
Cov.:
24
AF XY:
0.0743
AC XY:
52247
AN XY:
703602
show subpopulations
African (AFR)
AF:
0.0128
AC:
415
AN:
32434
American (AMR)
AF:
0.0878
AC:
3688
AN:
41988
Ashkenazi Jewish (ASJ)
AF:
0.0588
AC:
1501
AN:
25518
East Asian (EAS)
AF:
0.00803
AC:
315
AN:
39230
South Asian (SAS)
AF:
0.0292
AC:
2451
AN:
83856
European-Finnish (FIN)
AF:
0.0907
AC:
4791
AN:
52812
Middle Eastern (MID)
AF:
0.0145
AC:
82
AN:
5674
European-Non Finnish (NFE)
AF:
0.0839
AC:
89955
AN:
1072630
Other (OTH)
AF:
0.0631
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:
8509
AN:
152122
Hom.:
327
Cov.:
32
AF XY:
0.0552
AC XY:
4101
AN XY:
74360
show subpopulations
African (AFR)
AF:
0.0150
AC:
623
AN:
41526
American (AMR)
AF:
0.0598
AC:
915
AN:
15290
Ashkenazi Jewish (ASJ)
AF:
0.0588
AC:
204
AN:
3468
East Asian (EAS)
AF:
0.00946
AC:
49
AN:
5178
South Asian (SAS)
AF:
0.0251
AC:
121
AN:
4814
European-Finnish (FIN)
AF:
0.0929
AC:
982
AN:
10576
Middle Eastern (MID)
AF:
0.00680
AC:
2
AN:
294
European-Non Finnish (NFE)
AF:
0.0796
AC:
5410
AN:
67954
Other (OTH)
AF:
0.0530
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:
0.0396
Hom.:
40
Bravo
AF:
0.0542
Asia WGS
AF:
0.0230
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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
1.1
DANN
Benign
0.63
PhyloP100
-0.43
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs12434245; hg19: chr14-64691853; API