rs1152591

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.19057-64A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 1,612,370 control chromosomes in the GnomAD database, including 238,180 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 31859 hom., cov: 32)

Exomes 𝑓: 0.53 ( 206321 hom. )

Consequence

SYNE2
NM_182914.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.27

Publications

81 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=-0.94).

BP6

Variant 14-64214130-A-G is Benign according to our data. Variant chr14-64214130-A-G is described in ClinVar as Benign. ClinVar VariationId is 1258595.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.863 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SYNE2	NM_182914.3	MANE Select	c.19057-64A>G	intron	N/A	NP_878918.2	Q8WXH0-2
SYNE2	NM_015180.6		c.19057-64A>G	intron	N/A	NP_055995.4
SYNE2	NM_182913.4		c.-106A>G	upstream_gene	N/A	NP_878917.1	Q8WXH0-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SYNE2	ENST00000555002.6	TSL:1 MANE Select	c.19057-64A>G	intron	N/A	ENSP00000450831.2	Q8WXH0-2
SYNE2	ENST00000344113.8	TSL:1	c.19057-64A>G	intron	N/A	ENSP00000341781.4	Q8WXH0-1
SYNE2	ENST00000394768.6	TSL:1	n.8590-64A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.628

AC:

95413

AN:

151942

Hom.:

31806

Cov.:

show subpopulations

Gnomad AFR

AF:

0.871

Gnomad AMI

AF:

0.731

Gnomad AMR

AF:

0.544

Gnomad ASJ

AF:

0.615

Gnomad EAS

AF:

0.721

Gnomad SAS

AF:

0.516

Gnomad FIN

AF:

0.532

Gnomad MID

AF:

0.551

Gnomad NFE

AF:

0.515

Gnomad OTH

AF:

0.610

GnomAD4 exome

AF:

0.527

AC:

769658

AN:

1460310

Hom.:

206321

Cov.:

AF XY:

0.526

AC XY:

381820

AN XY:

726468

show subpopulations

African (AFR)

AF:

0.885

AC:

29520

AN:

33342

American (AMR)

AF:

0.516

AC:

22959

AN:

44494

Ashkenazi Jewish (ASJ)

AF:

0.617

AC:

16124

AN:

26120

East Asian (EAS)

AF:

0.683

AC:

27084

AN:

39682

South Asian (SAS)

AF:

0.505

AC:

43501

AN:

86134

European-Finnish (FIN)

AF:

0.523

AC:

27815

AN:

53234

Middle Eastern (MID)

AF:

0.565

AC:

3255

AN:

5758

European-Non Finnish (NFE)

AF:

0.509

AC:

565816

AN:

1111212

Other (OTH)

AF:

0.557

AC:

33584

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

20010

40020

60029

80039

100049

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16496

32992

49488

65984

82480

<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:

0.628

AC:

95522

AN:

152060

Hom.:

31859

Cov.:

AF XY:

0.624

AC XY:

46409

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.871

AC:

36135

AN:

41492

American (AMR)

AF:

0.544

AC:

8307

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.615

AC:

2134

AN:

3472

East Asian (EAS)

AF:

0.721

AC:

3727

AN:

5168

South Asian (SAS)

AF:

0.515

AC:

2484

AN:

4826

European-Finnish (FIN)

AF:

0.532

AC:

5619

AN:

10560

Middle Eastern (MID)

AF:

0.541

AC:

158

AN:

292

European-Non Finnish (NFE)

AF:

0.515

AC:

35008

AN:

67962

Other (OTH)

AF:

0.609

AC:

1283

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1660

3319

4979

6638

8298

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

762

1524

2286

3048

3810

<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:

0.560

Hom.:

70395

Bravo

AF:

0.643

Asia WGS

AF:

0.624

AC:

2169

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.049

(source)

DANN

Benign

0.29

PhyloP100

-2.3

PromoterAI

0.017

Neutral

(source)

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

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