14-64146127-C-T

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.15543C>T(p.Ile5181Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 1,600,702 control chromosomes in the GnomAD database, including 99,823 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. I5181I) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.40 ( 12615 hom., cov: 33)

Exomes 𝑓: 0.34 ( 87208 hom. )

Consequence

SYNE2
NM_182914.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.18

Publications

24 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: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ESR2 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_182914.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.54).

BP6

Variant 14-64146127-C-T is Benign according to our data. Variant chr14-64146127-C-T is described in ClinVar as Benign. ClinVar VariationId is 130479.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.18 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.522 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.15543C>T	p.Ile5181Ile	synonymous	Exon 84 of 116	NP_878918.2	Q8WXH0-2
	SYNE2	NM_015180.6		c.15543C>T	p.Ile5181Ile	synonymous	Exon 84 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.15543C>T	p.Ile5181Ile	synonymous	Exon 84 of 116	ENSP00000450831.2	Q8WXH0-2
SYNE2	ENST00000344113.8	TSL:1	c.15543C>T	p.Ile5181Ile	synonymous	Exon 84 of 115	ENSP00000341781.4	Q8WXH0-1
SYNE2	ENST00000394768.6	TSL:1	n.5076C>T		non_coding_transcript_exon	Exon 32 of 63

Frequencies

GnomAD3 genomes

AF:

0.399

AC:

60575

AN:

151854

Hom.:

12584

Cov.:

show subpopulations

Gnomad AFR

AF:

0.527

Gnomad AMI

AF:

0.332

Gnomad AMR

AF:

0.364

Gnomad ASJ

AF:

0.389

Gnomad EAS

AF:

0.511

Gnomad SAS

AF:

0.330

Gnomad FIN

AF:

0.360

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.333

Gnomad OTH

AF:

0.386

GnomAD2 exomes

AF:

0.367

AC:

90778

AN:

247578

AF XY:

0.359

show subpopulations

Gnomad AFR exome

AF:

0.540

Gnomad AMR exome

AF:

0.385

Gnomad ASJ exome

AF:

0.389

Gnomad EAS exome

AF:

0.514

Gnomad FIN exome

AF:

0.348

Gnomad NFE exome

AF:

0.327

Gnomad OTH exome

AF:

0.342

GnomAD4 exome

AF:

0.343

AC:

496430

AN:

1448730

Hom.:

87208

Cov.:

AF XY:

0.342

AC XY:

246400

AN XY:

721256

show subpopulations

African (AFR)

AF:

0.536

AC:

17691

AN:

33022

American (AMR)

AF:

0.382

AC:

16715

AN:

43748

Ashkenazi Jewish (ASJ)

AF:

0.382

AC:

9919

AN:

25958

East Asian (EAS)

AF:

0.498

AC:

19604

AN:

39402

South Asian (SAS)

AF:

0.326

AC:

27763

AN:

85174

European-Finnish (FIN)

AF:

0.349

AC:

18602

AN:

53254

Middle Eastern (MID)

AF:

0.324

AC:

1859

AN:

5740

European-Non Finnish (NFE)

AF:

0.329

AC:

362840

AN:

1102560

Other (OTH)

AF:

0.358

AC:

21437

AN:

59872

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.434

Heterozygous variant carriers

14878

29757

44635

59514

74392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11918

23836

35754

47672

59590

<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:

0.399

AC:

60662

AN:

151972

Hom.:

12615

Cov.:

AF XY:

0.398

AC XY:

29583

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.528

AC:

21864

AN:

41434

American (AMR)

AF:

0.364

AC:

5568

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.389

AC:

1351

AN:

3470

East Asian (EAS)

AF:

0.511

AC:

2644

AN:

5170

South Asian (SAS)

AF:

0.330

AC:

1590

AN:

4820

European-Finnish (FIN)

AF:

0.360

AC:

3794

AN:

10528

Middle Eastern (MID)

AF:

0.330

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.333

AC:

22636

AN:

67960

Other (OTH)

AF:

0.387

AC:

817

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1825

3650

5475

7300

9125

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

568

1136

1704

2272

2840

<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:

0.354

Hom.:

15184

Bravo

AF:

0.409

Asia WGS

AF:

0.418

AC:

1449

AN:

3478

ClinVar

ClinVar submissions

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)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

1.6

(source)

DANN

Benign

0.59

PhyloP100

-1.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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