14-64139936-G-C

Position:

chr14-64139936-G-C

Variant summary

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

The NM_182914.3(SYNE2):c.14844-5G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,613,276 control chromosomes in the GnomAD database, including 9,708 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 0.090 ( 831 hom., cov: 32)

Exomes 𝑓: 0.10 ( 8877 hom. )

Consequence

SYNE2
NM_182914.3 splice_region, intron

Scores

Splicing: ADA: 0.00001197

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.475

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 14-64139936-G-C is Benign according to our data. Variant chr14-64139936-G-C is described in ClinVar as [Benign]. Clinvar id is 130478.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-64139936-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNE2	NM_182914.3 link	c.14844-5G>C		splice_region_variant, intron_variant		ENST00000555002.6	NP_878918.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNE2	ENST00000555002.6 link	c.14844-5G>C		splice_region_variant, intron_variant		1	NM_182914.3	ENSP00000450831.2		Q8WXH0-2A0A0C4DGK3

Frequencies

GnomAD3 genomes

AF:

0.0903

AC:

13736

AN:

152080

Hom.:

831

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0277

Gnomad AMI

AF:

0.0954

Gnomad AMR

AF:

0.0983

Gnomad ASJ

AF:

0.0649

Gnomad EAS

AF:

0.243

Gnomad SAS

AF:

0.0622

Gnomad FIN

AF:

0.173

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.0839

GnomAD3 exomes

AF:

0.110

AC:

27531

AN:

251256

Hom.:

1861

AF XY:

0.107

AC XY:

14561

AN XY:

135792

show subpopulations

Gnomad AFR exome

AF:

0.0281

Gnomad AMR exome

AF:

0.122

Gnomad ASJ exome

AF:

0.0680

Gnomad EAS exome

AF:

0.241

Gnomad SAS exome

AF:

0.0699

Gnomad FIN exome

AF:

0.157

Gnomad NFE exome

AF:

0.102

Gnomad OTH exome

AF:

0.0969

GnomAD4 exome

AF:

0.104

AC:

152624

AN:

1461078

Hom.:

8877

Cov.:

AF XY:

0.104

AC XY:

75385

AN XY:

726878

show subpopulations

Gnomad4 AFR exome

AF:

0.0252

Gnomad4 AMR exome

AF:

0.120

Gnomad4 ASJ exome

AF:

0.0649

Gnomad4 EAS exome

AF:

0.221

Gnomad4 SAS exome

AF:

0.0688

Gnomad4 FIN exome

AF:

0.160

Gnomad4 NFE exome

AF:

0.104

Gnomad4 OTH exome

AF:

0.0994

GnomAD4 genome

AF:

0.0902

AC:

13733

AN:

152198

Hom.:

831

Cov.:

AF XY:

0.0935

AC XY:

6957

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.0276

Gnomad4 AMR

AF:

0.0983

Gnomad4 ASJ

AF:

0.0649

Gnomad4 EAS

AF:

0.243

Gnomad4 SAS

AF:

0.0625

Gnomad4 FIN

AF:

0.173

Gnomad4 NFE

AF:

0.106

Gnomad4 OTH

AF:

0.0825

Alfa

AF:

0.0795

Hom.:

208

Bravo

AF:

0.0836

Asia WGS

AF:

0.128

AC:

444

AN:

3478

EpiCase

AF:

0.0893

EpiControl

AF:

0.0926

ClinVar

Significance: Benign

Submissions summary: Benign:5

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	- -

Emery-Dreifuss muscular dystrophy 5, autosomal dominant

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Aug 15, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.028

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000012

dbscSNV1_RF

Benign

0.0060

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