rs7140414

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.13423-7C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0054 in 1,613,968 control chromosomes in the GnomAD database, including 416 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 228 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 188 hom. )

Consequence

SYNE2
NM_182914.3 splice_region, intron

Scores

Splicing: ADA: 0.001296

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.0770

Publications

3 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 14-64125072-C-G is Benign according to our data. Variant chr14-64125072-C-G is described in ClinVar as Benign. ClinVar VariationId is 130473.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0972 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.13423-7C>G		splice_region intron	N/A	NP_878918.2	Q8WXH0-2
	SYNE2	NM_015180.6		c.13423-7C>G		splice_region intron	N/A	NP_055995.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SYNE2	ENST00000555002.6	TSL:1 MANE Select	c.13423-7C>G	splice_region intron	N/A	ENSP00000450831.2	Q8WXH0-2
SYNE2	ENST00000344113.8	TSL:1	c.13423-7C>G	splice_region intron	N/A	ENSP00000341781.4	Q8WXH0-1
SYNE2	ENST00000394768.6	TSL:1	n.2956-7C>G	splice_region intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0286

AC:

4351

AN:

152098

Hom.:

225

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0995

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00983

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.0234

GnomAD2 exomes

AF:

0.00746

AC:

1876

AN:

251386

AF XY:

0.00526

show subpopulations

Gnomad AFR exome

AF:

0.102

Gnomad AMR exome

AF:

0.00425

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000255

Gnomad OTH exome

AF:

0.00424

GnomAD4 exome

AF:

0.00297

AC:

4340

AN:

1461752

Hom.:

188

Cov.:

AF XY:

0.00257

AC XY:

1871

AN XY:

727182

show subpopulations

African (AFR)

AF:

0.102

AC:

3418

AN:

33460

American (AMR)

AF:

0.00543

AC:

243

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.000230

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.000290

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.00763

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000182

AC:

202

AN:

1111950

Other (OTH)

AF:

0.00666

AC:

402

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

201

402

603

804

1005

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

106

212

318

424

530

<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:

0.0287

AC:

4375

AN:

152216

Hom.:

228

Cov.:

AF XY:

0.0273

AC XY:

2029

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0998

AC:

4142

AN:

41512

American (AMR)

AF:

0.00982

AC:

150

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000415

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000426

AC:

AN:

68010

Other (OTH)

AF:

0.0232

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

197

395

592

790

987

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<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:

0.00849

Hom.:

Bravo

AF:

0.0324

Asia WGS

AF:

0.00577

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000474

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 (3)

not specified (3)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.4

(source)

DANN

Benign

0.65

PhyloP100

0.077

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0013

dbscSNV1_RF

Benign

0.042

SpliceAI score (max)

0.040

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

Computational scores

Splicing

Publications

Other links and lift over