Variant chr14-64107422-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_182914.3(SYNE2):c.12493-69C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0986 in 1,346,174 control chromosomes in the GnomAD database, including 9,589 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1739 hom., cov: 32)

Exomes 𝑓: 0.094 ( 7850 hom. )

Consequence

SYNE2
NM_182914.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.34

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 14-64107422-C-A is Benign according to our data. Variant chr14-64107422-C-A is described in ClinVar as [Benign]. Clinvar id is 1179269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNE2	NM_182914.3 linkuse as main transcript	c.12493-69C>A		intron_variant		ENST00000555002.6	NP_878918.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNE2	ENST00000555002.6 linkuse as main transcript	c.12493-69C>A		intron_variant		1	NM_182914.3	ENSP00000450831	P4	Q8WXH0-2

Frequencies

GnomAD3 genomes

AF:

0.133

AC:

20162

AN:

151926

Hom.:

1737

Cov.:

show subpopulations

Gnomad AFR

AF:

0.195

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.161

Gnomad ASJ

AF:

0.120

Gnomad EAS

AF:

0.377

Gnomad SAS

AF:

0.188

Gnomad FIN

AF:

0.103

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0730

Gnomad OTH

AF:

0.132

GnomAD4 exome

AF:

0.0943

AC:

112553

AN:

1194130

Hom.:

7850

AF XY:

0.0972

AC XY:

58980

AN XY:

606814

show subpopulations

Gnomad4 AFR exome

AF:

0.200

Gnomad4 AMR exome

AF:

0.164

Gnomad4 ASJ exome

AF:

0.126

Gnomad4 EAS exome

AF:

0.340

Gnomad4 SAS exome

AF:

0.182

Gnomad4 FIN exome

AF:

0.0961

Gnomad4 NFE exome

AF:

0.0659

Gnomad4 OTH exome

AF:

0.116

GnomAD4 genome

AF:

0.133

AC:

20191

AN:

152044

Hom.:

1739

Cov.:

AF XY:

0.139

AC XY:

10319

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.195

Gnomad4 AMR

AF:

0.161

Gnomad4 ASJ

AF:

0.120

Gnomad4 EAS

AF:

0.377

Gnomad4 SAS

AF:

0.188

Gnomad4 FIN

AF:

0.103

Gnomad4 NFE

AF:

0.0730

Gnomad4 OTH

AF:

0.131

Alfa

AF:

0.0868

Hom.:

1287

Bravo

AF:

0.138

Asia WGS

AF:

0.237

AC:

823

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

-0.82

CADD

Benign

0.23

DANN

Benign

0.36

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