rs17101637

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_182914.3(SYNE2):c.11613A>G(p.Val3871Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0762 in 1,613,930 control chromosomes in the GnomAD database, including 5,365 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 992 hom., cov: 32)

Exomes 𝑓: 0.073 ( 4373 hom. )

Consequence

SYNE2
NM_182914.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.543

Publications

12 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]

SYNE2 links:

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)

ESR2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 14-64087799-A-G is Benign according to our data. Variant chr14-64087799-A-G is described in ClinVar as Benign. ClinVar VariationId is 130459.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.543 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182914.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE2	NM_182914.3	MANE Select	c.11613A>G	p.Val3871Val	synonymous	Exon 58 of 116	NP_878918.2
	SYNE2	NM_015180.6		c.11613A>G	p.Val3871Val	synonymous	Exon 58 of 115	NP_055995.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SYNE2	ENST00000555002.6	TSL:1 MANE Select	c.11613A>G	p.Val3871Val	synonymous	Exon 58 of 116	ENSP00000450831.2
SYNE2	ENST00000344113.8	TSL:1	c.11613A>G	p.Val3871Val	synonymous	Exon 58 of 115	ENSP00000341781.4
SYNE2	ENST00000394768.6	TSL:1	n.1146A>G		non_coding_transcript_exon	Exon 6 of 63

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

15941

AN:

152154

Hom.:

984

Cov.:

show subpopulations

Gnomad AFR

AF:

0.171

Gnomad AMI

AF:

0.104

Gnomad AMR

AF:

0.112

Gnomad ASJ

AF:

0.0844

Gnomad EAS

AF:

0.0504

Gnomad SAS

AF:

0.0617

Gnomad FIN

AF:

0.0869

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.0741

Gnomad OTH

AF:

0.0973

GnomAD2 exomes

AF:

0.0832

AC:

20879

AN:

250920

AF XY:

0.0798

show subpopulations

Gnomad AFR exome

AF:

0.168

Gnomad AMR exome

AF:

0.117

Gnomad ASJ exome

AF:

0.0846

Gnomad EAS exome

AF:

0.0492

Gnomad FIN exome

AF:

0.0798

Gnomad NFE exome

AF:

0.0728

Gnomad OTH exome

AF:

0.0866

GnomAD4 exome

AF:

0.0732

AC:

106938

AN:

1461658

Hom.:

4373

Cov.:

AF XY:

0.0726

AC XY:

52813

AN XY:

727118

show subpopulations

African (AFR)

AF:

0.180

AC:

6024

AN:

33478

American (AMR)

AF:

0.118

AC:

5273

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0794

AC:

2076

AN:

26134

East Asian (EAS)

AF:

0.0529

AC:

2097

AN:

39666

South Asian (SAS)

AF:

0.0595

AC:

5136

AN:

86256

European-Finnish (FIN)

AF:

0.0759

AC:

4052

AN:

53414

Middle Eastern (MID)

AF:

0.0922

AC:

532

AN:

5768

European-Non Finnish (NFE)

AF:

0.0693

AC:

77031

AN:

1111834

Other (OTH)

AF:

0.0781

AC:

4717

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

5024

10048

15072

20096

25120

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2878

5756

8634

11512

14390

<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:

0.105

AC:

15997

AN:

152272

Hom.:

992

Cov.:

AF XY:

0.105

AC XY:

7838

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.172

AC:

7130

AN:

41546

American (AMR)

AF:

0.112

AC:

1712

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0844

AC:

293

AN:

3472

East Asian (EAS)

AF:

0.0503

AC:

261

AN:

5186

South Asian (SAS)

AF:

0.0619

AC:

299

AN:

4828

European-Finnish (FIN)

AF:

0.0869

AC:

922

AN:

10606

Middle Eastern (MID)

AF:

0.119

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0741

AC:

5041

AN:

68020

Other (OTH)

AF:

0.0991

AC:

209

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

722

1444

2166

2888

3610

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

344

516

688

860

<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:

0.0830

Hom.:

2513

Bravo

AF:

0.109

Asia WGS

AF:

0.0860

AC:

298

AN:

3478

EpiCase

AF:

0.0684

EpiControl

AF:

0.0717

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Emery-Dreifuss muscular dystrophy 5, autosomal dominant (2)

not provided (2)

not specified (1)

SYNE2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.9

(source)

DANN

Benign

0.67

PhyloP100

-0.54

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over