Variant rs186427714 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_182914.3(SYNE2):c.5395T>C(p.Leu1799=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000357 in 1,613,970 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 1 hom. )

Consequence

SYNE2
NM_182914.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.269

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 14-64021899-T-C is Benign according to our data. Variant chr14-64021899-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 282118.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.269 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00192 (292/152340) while in subpopulation AFR AF= 0.00674 (280/41572). AF 95% confidence interval is 0.00609. There are 2 homozygotes in gnomad4. There are 137 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 292 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE2	NM_182914.3 linkuse as main transcript	c.5395T>C	p.Leu1799=	synonymous_variant	37/116	ENST00000555002.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE2	ENST00000555002.6 linkuse as main transcript	c.5395T>C	p.Leu1799=	synonymous_variant	37/116	1	NM_182914.3	P4	Q8WXH0-2

Frequencies

GnomAD3 genomes

AF:

0.00192

AC:

292

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000510

AC:

127

AN:

249260

Hom.:

AF XY:

0.000458

AC XY:

AN XY:

135266

show subpopulations

Gnomad AFR exome

AF:

0.00678

Gnomad AMR exome

AF:

0.000492

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000194

AC:

284

AN:

1461630

Hom.:

Cov.:

AF XY:

0.000168

AC XY:

122

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.00619

Gnomad4 AMR exome

AF:

0.000537

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.000563

GnomAD4 genome

AF:

0.00192

AC:

292

AN:

152340

Hom.:

Cov.:

AF XY:

0.00184

AC XY:

137

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00674

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00118

Hom.:

Bravo

AF:

0.00208

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jul 22, 2015

- -

Emery-Dreifuss muscular dystrophy 5, autosomal dominant

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 16, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.6

DANN

Benign

0.74

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