rs7161192

Variant names:

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.17202C>A(p.Leu5734Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 1,612,700 control chromosomes in the GnomAD database, including 85,557 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 8715 hom., cov: 32)

Exomes 𝑓: 0.32 ( 76842 hom. )

Consequence

SYNE2
NM_182914.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.220

Publications

26 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=-0.53).

BP6

Variant 14-64170429-C-A is Benign according to our data. Variant chr14-64170429-C-A is described in ClinVar as Benign. ClinVar VariationId is 130485.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.22 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.55 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.17202C>A	p.Leu5734Leu	synonymous	Exon 94 of 116	NP_878918.2	Q8WXH0-2
	SYNE2	NM_015180.6		c.17202C>A	p.Leu5734Leu	synonymous	Exon 94 of 115	NP_055995.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SYNE2	ENST00000555002.6	TSL:1 MANE Select	c.17202C>A	p.Leu5734Leu	synonymous	Exon 94 of 116	ENSP00000450831.2	Q8WXH0-2
SYNE2	ENST00000344113.8	TSL:1	c.17202C>A	p.Leu5734Leu	synonymous	Exon 94 of 115	ENSP00000341781.4	Q8WXH0-1
SYNE2	ENST00000394768.6	TSL:1	n.6735C>A		non_coding_transcript_exon	Exon 42 of 63

Frequencies

GnomAD3 genomes

AF:

0.335

AC:

50949

AN:

151914

Hom.:

8715

Cov.:

show subpopulations

Gnomad AFR

AF:

0.351

Gnomad AMI

AF:

0.290

Gnomad AMR

AF:

0.291

Gnomad ASJ

AF:

0.376

Gnomad EAS

AF:

0.566

Gnomad SAS

AF:

0.288

Gnomad FIN

AF:

0.338

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.320

Gnomad OTH

AF:

0.318

GnomAD2 exomes

AF:

0.329

AC:

81919

AN:

249010

AF XY:

0.327

show subpopulations

Gnomad AFR exome

AF:

0.358

Gnomad AMR exome

AF:

0.260

Gnomad ASJ exome

AF:

0.376

Gnomad EAS exome

AF:

0.572

Gnomad FIN exome

AF:

0.328

Gnomad NFE exome

AF:

0.315

Gnomad OTH exome

AF:

0.314

GnomAD4 exome

AF:

0.321

AC:

469584

AN:

1460668

Hom.:

76842

Cov.:

AF XY:

0.321

AC XY:

233105

AN XY:

726548

show subpopulations

African (AFR)

AF:

0.353

AC:

11818

AN:

33470

American (AMR)

AF:

0.266

AC:

11832

AN:

44514

Ashkenazi Jewish (ASJ)

AF:

0.367

AC:

9567

AN:

26094

East Asian (EAS)

AF:

0.540

AC:

21411

AN:

39676

South Asian (SAS)

AF:

0.287

AC:

24691

AN:

86086

European-Finnish (FIN)

AF:

0.332

AC:

17693

AN:

53326

Middle Eastern (MID)

AF:

0.302

AC:

1740

AN:

5766

European-Non Finnish (NFE)

AF:

0.316

AC:

350900

AN:

1111380

Other (OTH)

AF:

0.330

AC:

19932

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

18417

36834

55251

73668

92085

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11576

23152

34728

46304

57880

<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:

0.335

AC:

50975

AN:

152032

Hom.:

8715

Cov.:

AF XY:

0.336

AC XY:

24952

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.351

AC:

14568

AN:

41468

American (AMR)

AF:

0.291

AC:

4446

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.376

AC:

1303

AN:

3468

East Asian (EAS)

AF:

0.567

AC:

2925

AN:

5162

South Asian (SAS)

AF:

0.288

AC:

1387

AN:

4816

European-Finnish (FIN)

AF:

0.338

AC:

3564

AN:

10560

Middle Eastern (MID)

AF:

0.299

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.320

AC:

21767

AN:

67958

Other (OTH)

AF:

0.314

AC:

663

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1702

3405

5107

6810

8512

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

510

1020

1530

2040

2550

<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:

0.328

Hom.:

39729

Bravo

AF:

0.336

Asia WGS

AF:

0.371

AC:

1287

AN:

3478

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 (3)

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

6.3

(source)

DANN

Benign

0.76

PhyloP100

0.22

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