Variant chr14-64225135-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_182914.3(SYNE2):c.20516+90C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0737 in 1,564,992 control chromosomes in the GnomAD database, including 4,934 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.056 ( 327 hom., cov: 32)

Exomes 𝑓: 0.076 ( 4607 hom. )

Consequence

SYNE2
NM_182914.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.435

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 14-64225135-C-T is Benign according to our data. Variant chr14-64225135-C-T is described in ClinVar as [Benign]. Clinvar id is 1295983.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE2	NM_182914.3 linkuse as main transcript	c.20516+90C>T		intron_variant		ENST00000555002.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE2	ENST00000555002.6 linkuse as main transcript	c.20516+90C>T		intron_variant		1	NM_182914.3	P4	Q8WXH0-2

Frequencies

GnomAD3 genomes

AF:

0.0559

AC:

8502

AN:

152004

Hom.:

326

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0150

Gnomad AMI

AF:

0.100

Gnomad AMR

AF:

0.0596

Gnomad ASJ

AF:

0.0588

Gnomad EAS

AF:

0.00906

Gnomad SAS

AF:

0.0251

Gnomad FIN

AF:

0.0929

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0796

Gnomad OTH

AF:

0.0536

GnomAD4 exome

AF:

0.0757

AC:

106903

AN:

1412870

Hom.:

4607

Cov.:

AF XY:

0.0743

AC XY:

52247

AN XY:

703602

show subpopulations

Gnomad4 AFR exome

AF:

0.0128

Gnomad4 AMR exome

AF:

0.0878

Gnomad4 ASJ exome

AF:

0.0588

Gnomad4 EAS exome

AF:

0.00803

Gnomad4 SAS exome

AF:

0.0292

Gnomad4 FIN exome

AF:

0.0907

Gnomad4 NFE exome

AF:

0.0839

Gnomad4 OTH exome

AF:

0.0631

GnomAD4 genome

AF:

0.0559

AC:

8509

AN:

152122

Hom.:

327

Cov.:

AF XY:

0.0552

AC XY:

4101

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0150

Gnomad4 AMR

AF:

0.0598

Gnomad4 ASJ

AF:

0.0588

Gnomad4 EAS

AF:

0.00946

Gnomad4 SAS

AF:

0.0251

Gnomad4 FIN

AF:

0.0929

Gnomad4 NFE

AF:

0.0796

Gnomad4 OTH

AF:

0.0530

Alfa

AF:

0.0400

Hom.:

Bravo

AF:

0.0542

Asia WGS

AF:

0.0230

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.1

DANN

Benign

0.63

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over