Variant 14-64214130-A-G 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.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

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=-0.94).

BP6

Variant 14-64214130-A-G is Benign according to our data. Variant chr14-64214130-A-G is described in ClinVar as [Benign]. Clinvar id is 1258595.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-64214130-A-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.863 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.19057-64A>G		intron_variant		ENST00000555002.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE2	ENST00000555002.6 linkuse as main transcript	c.19057-64A>G		intron_variant		1	NM_182914.3	P4	Q8WXH0-2

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

Gnomad4 AFR exome

AF:

0.885

Gnomad4 AMR exome

AF:

0.516

Gnomad4 ASJ exome

AF:

0.617

Gnomad4 EAS exome

AF:

0.683

Gnomad4 SAS exome

AF:

0.505

Gnomad4 FIN exome

AF:

0.523

Gnomad4 NFE exome

AF:

0.509

Gnomad4 OTH exome

AF:

0.557

GnomAD4 genome

AF:

0.628

AC:

95522

AN:

152060

Hom.:

31859

Cov.:

AF XY:

0.624

AC XY:

46409

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.871

Gnomad4 AMR

AF:

0.544

Gnomad4 ASJ

AF:

0.615

Gnomad4 EAS

AF:

0.721

Gnomad4 SAS

AF:

0.515

Gnomad4 FIN

AF:

0.532

Gnomad4 NFE

AF:

0.515

Gnomad4 OTH

AF:

0.609

Alfa

AF:

0.532

Hom.:

34666

Bravo

AF:

0.643

Asia WGS

AF:

0.624

AC:

2169

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

-0.94

CADD

Benign

0.049

DANN

Benign

0.29

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