rs2256191

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.17938T>C(p.Leu5980Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 1,613,720 control chromosomes in the GnomAD database, including 119,799 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 18869 hom., cov: 31)

Exomes 𝑓: 0.36 ( 100930 hom. )

Consequence

SYNE2
NM_182914.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.100

Publications

28 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=-0.57).

BP6

Variant 14-64190137-T-C is Benign according to our data. Variant chr14-64190137-T-C is described in ClinVar as Benign. ClinVar VariationId is 130488.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.1 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.739 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE2	NM_182914.3	MANE Select	c.17938T>C	p.Leu5980Leu	synonymous	Exon 99 of 116	NP_878918.2
	SYNE2	NM_015180.6		c.17938T>C	p.Leu5980Leu	synonymous	Exon 99 of 115	NP_055995.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SYNE2	ENST00000555002.6	TSL:1 MANE Select	c.17938T>C	p.Leu5980Leu	synonymous	Exon 99 of 116	ENSP00000450831.2
SYNE2	ENST00000344113.8	TSL:1	c.17938T>C	p.Leu5980Leu	synonymous	Exon 99 of 115	ENSP00000341781.4
SYNE2	ENST00000394768.6	TSL:1	n.7471T>C		non_coding_transcript_exon	Exon 47 of 63

Frequencies

GnomAD3 genomes

AF:

0.465

AC:

70641

AN:

151804

Hom.:

18831

Cov.:

show subpopulations

Gnomad AFR

AF:

0.745

Gnomad AMI

AF:

0.375

Gnomad AMR

AF:

0.389

Gnomad ASJ

AF:

0.494

Gnomad EAS

AF:

0.369

Gnomad SAS

AF:

0.396

Gnomad FIN

AF:

0.274

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.354

Gnomad OTH

AF:

0.463

GnomAD2 exomes

AF:

0.388

AC:

97453

AN:

251396

AF XY:

0.382

show subpopulations

Gnomad AFR exome

AF:

0.754

Gnomad AMR exome

AF:

0.357

Gnomad ASJ exome

AF:

0.492

Gnomad EAS exome

AF:

0.383

Gnomad FIN exome

AF:

0.286

Gnomad NFE exome

AF:

0.355

Gnomad OTH exome

AF:

0.371

GnomAD4 exome

AF:

0.364

AC:

531648

AN:

1461796

Hom.:

100930

Cov.:

AF XY:

0.364

AC XY:

264385

AN XY:

727206

show subpopulations

African (AFR)

AF:

0.758

AC:

25386

AN:

33480

American (AMR)

AF:

0.360

AC:

16099

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.491

AC:

12843

AN:

26134

East Asian (EAS)

AF:

0.356

AC:

14138

AN:

39698

South Asian (SAS)

AF:

0.393

AC:

33870

AN:

86256

European-Finnish (FIN)

AF:

0.284

AC:

15190

AN:

53418

Middle Eastern (MID)

AF:

0.439

AC:

2530

AN:

5766

European-Non Finnish (NFE)

AF:

0.349

AC:

387977

AN:

1111934

Other (OTH)

AF:

0.391

AC:

23615

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

19400

38800

58199

77599

96999

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12592

25184

37776

50368

62960

<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:

0.466

AC:

70728

AN:

151924

Hom.:

18869

Cov.:

AF XY:

0.458

AC XY:

34003

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.746

AC:

30877

AN:

41402

American (AMR)

AF:

0.388

AC:

5929

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.494

AC:

1715

AN:

3470

East Asian (EAS)

AF:

0.369

AC:

1909

AN:

5172

South Asian (SAS)

AF:

0.396

AC:

1904

AN:

4812

European-Finnish (FIN)

AF:

0.274

AC:

2885

AN:

10528

Middle Eastern (MID)

AF:

0.493

AC:

145

AN:

294

European-Non Finnish (NFE)

AF:

0.354

AC:

24060

AN:

67964

Other (OTH)

AF:

0.457

AC:

963

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1676

3351

5027

6702

8378

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

620

1240

1860

2480

3100

<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:

0.405

Hom.:

46273

Bravo

AF:

0.487

Asia WGS

AF:

0.384

AC:

1334

AN:

3478

EpiCase

AF:

0.369

EpiControl

AF:

0.376

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 (4)

not provided (3)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.30

(source)

DANN

Benign

0.53

PhyloP100

-0.10

Mutation Taster

=97/3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over