Variant chr14-63852971-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The ENST00000674003.1(SYNE2):c.-52+218C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.021 in 151,768 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 43 hom., cov: 32)

Exomes 𝑓: 0.056 ( 0 hom. )

Consequence

SYNE2
ENST00000674003.1 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.186

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP6

Variant 14-63852971-C-T is Benign according to our data. Variant chr14-63852971-C-T is described in ClinVar as [Benign]. Clinvar id is 313475.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0209 (3164/151390) while in subpopulation AMR AF= 0.0337 (513/15220). AF 95% confidence interval is 0.0313. There are 43 homozygotes in gnomad4. There are 1574 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3164 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNE2	NM_182914.3 linkuse as main transcript	c.-224C>T		upstream_gene_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.-224C>T		upstream_gene_variant		1	NM_182914.3	ENSP00000450831.2		Q8WXH0-2A0A0C4DGK3

Frequencies

GnomAD3 genomes

AF:

0.0208

AC:

3150

AN:

151280

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00908

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0337

Gnomad ASJ

AF:

0.0344

Gnomad EAS

AF:

0.000585

Gnomad SAS

AF:

0.0338

Gnomad FIN

AF:

0.00540

Gnomad MID

AF:

0.0290

Gnomad NFE

AF:

0.0271

Gnomad OTH

AF:

0.0303

GnomAD4 exome

AF:

0.0556

AC:

AN:

378

Hom.:

Cov.:

AF XY:

0.0647

AC XY:

AN XY:

278

show subpopulations

Gnomad4 AFR exome

AF:

0.167

Gnomad4 AMR exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0469

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0536

Gnomad4 OTH exome

AF:

0.200

GnomAD4 genome

AF:

0.0209

AC:

3164

AN:

151390

Hom.:

Cov.:

AF XY:

0.0213

AC XY:

1574

AN XY:

73990

show subpopulations

Gnomad4 AFR

AF:

0.00940

Gnomad4 AMR

AF:

0.0337

Gnomad4 ASJ

AF:

0.0344

Gnomad4 EAS

AF:

0.000587

Gnomad4 SAS

AF:

0.0332

Gnomad4 FIN

AF:

0.00540

Gnomad4 NFE

AF:

0.0271

Gnomad4 OTH

AF:

0.0310

Alfa

AF:

0.0228

Hom.:

Bravo

AF:

0.0207

Asia WGS

AF:

0.0240

AC:

AN:

3348

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Emery-Dreifuss muscular dystrophy 5, autosomal dominant

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

0.98

Splicing

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