14-64027560-C-T

Variant names:

• chr14-64027560-C-T
• rs10151127
• NM_182914.3:c.6481C>T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_182914.3(SYNE2):​c.6481C>T​(p.Leu2161Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.898 in 1,612,324 control chromosomes in the GnomAD database, including 656,083 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.81 (52057 hom., cov: 33)
  • Exomes 𝑓: 0.91 (604026 hom.)
• Consequence: SYNE2 NM_182914.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.526

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 14-64027560-C-T is Benign according to our data. Variant chr14-64027560-C-T is described in ClinVar as [Benign]. Clinvar id is 130503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-64027560-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.526 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE2	NM_182914.3	c.6481C>T	p.Leu2161Leu	synonymous_variant	Exon 43 of 116	ENST00000555002.6	NP_878918.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE2	ENST00000555002.6	c.6481C>T	p.Leu2161Leu	synonymous_variant	Exon 43 of 116	1	NM_182914.3	ENSP00000450831.2

Frequencies

GnomAD3 genomes AF: 0.813 AC: 123587 AN: 152042 Hom.: 52047 Cov.: 33

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.924

Gnomad AMR AF: 0.880

Gnomad ASJ AF: 0.854

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.821

Gnomad FIN AF: 0.927

Gnomad MID AF: 0.822

Gnomad NFE AF: 0.925

Gnomad OTH AF: 0.828

GnomAD3 exomes AF: 0.877 AC: 218492 AN: 249248 Hom.: 96907 AF XY: 0.879 AC XY: 118931 AN XY: 135238

Gnomad AFR exome AF: 0.546

Gnomad AMR exome AF: 0.930

Gnomad ASJ exome AF: 0.837

Gnomad EAS exome AF: 0.833

Gnomad SAS exome AF: 0.831

Gnomad FIN exome AF: 0.924

Gnomad NFE exome AF: 0.919

Gnomad OTH exome AF: 0.874

GnomAD4 exome AF: 0.907 AC: 1324249 AN: 1460164 Hom.: 604026 Cov.: 38 AF XY: 0.905 AC XY: 657603 AN XY: 726348

Gnomad4 AFR exome AF: 0.534

Gnomad4 AMR exome AF: 0.925

Gnomad4 ASJ exome AF: 0.838

Gnomad4 EAS exome AF: 0.830

Gnomad4 SAS exome AF: 0.833

Gnomad4 FIN exome AF: 0.927

Gnomad4 NFE exome AF: 0.928

Gnomad4 OTH exome AF: 0.878

GnomAD4 genome AF: 0.813 AC: 123636 AN: 152160 Hom.: 52057 Cov.: 33 AF XY: 0.814 AC XY: 60551 AN XY: 74402

Gnomad4 AFR AF: 0.563

Gnomad4 AMR AF: 0.881

Gnomad4 ASJ AF: 0.854

Gnomad4 EAS AF: 0.842

Gnomad4 SAS AF: 0.822

Gnomad4 FIN AF: 0.927

Gnomad4 NFE AF: 0.925

Gnomad4 OTH AF: 0.826

Alfa AF: 0.862 Hom.: 25684

Bravo AF: 0.798

Asia WGS AF: 0.810 AC: 2818 AN: 3478

EpiCase AF: 0.916

EpiControl AF: 0.911

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Emery-Dreifuss muscular dystrophy 5, autosomal dominant Benign:3

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:2

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 06, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	7.4
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

Other links and lift over

dbSNP: rs10151127; hg19: chr14-64494278;