chr14-64026647-C-T

Position:

• chr14-64026647-C-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.6321C>T​(p.Ser2107Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00278 in 1,613,340 control chromosomes in the GnomAD database, including 157 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0046 (21 hom., cov: 33)
  • Exomes 𝑓: 0.0026 (136 hom.)
• Consequence: SYNE2 NM_182914.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.0860

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 14-64026647-C-T is Benign according to our data. Variant chr14-64026647-C-T is described in ClinVar as [Benign]. Clinvar id is 130502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.086 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNE2	NM_182914.3	c.6321C>T	p.Ser2107Ser	synonymous_variant	42/116	ENST00000555002.6	NP_878918.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNE2	ENST00000555002.6	c.6321C>T	p.Ser2107Ser	synonymous_variant	42/116	1	NM_182914.3	ENSP00000450831.2

Frequencies

GnomAD3 genomes AF: 0.00456 AC: 694 AN: 152148 Hom.: 21 Cov.: 33

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0398

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00693

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00765

GnomAD3 exomes AF: 0.0105 AC: 2615 AN: 248372 Hom.: 94 AF XY: 0.00770 AC XY: 1037 AN XY: 134754

Gnomad AFR exome AF: 0.000648

Gnomad AMR exome AF: 0.0696

Gnomad ASJ exome AF: 0.0000995

Gnomad EAS exome AF: 0.00792

Gnomad SAS exome AF: 0.000427

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.000133

Gnomad OTH exome AF: 0.00663

GnomAD4 exome AF: 0.00260 AC: 3795 AN: 1461074 Hom.: 136 Cov.: 31 AF XY: 0.00219 AC XY: 1595 AN XY: 726794

Gnomad4 AFR exome AF: 0.000299

Gnomad4 AMR exome AF: 0.0674

Gnomad4 ASJ exome AF: 0.0000765

Gnomad4 EAS exome AF: 0.0125

Gnomad4 SAS exome AF: 0.000290

Gnomad4 FIN exome AF: 0.000206

Gnomad4 NFE exome AF: 0.000112

Gnomad4 OTH exome AF: 0.00202

GnomAD4 genome AF: 0.00457 AC: 696 AN: 152266 Hom.: 21 Cov.: 33 AF XY: 0.00514 AC XY: 383 AN XY: 74458

Gnomad4 AFR AF: 0.000409

Gnomad4 AMR AF: 0.0398

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00714

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00757

Alfa AF: 0.00108 Hom.: 1

Bravo AF: 0.00829

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 14, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 23, 2015	- -

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 13, 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 26, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.1
DANN	Benign	0.20
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs143410137; hg19: chr14-64493365;