rs17101525

Variant names:

• chr14-63990506-C-A
• rs17101525
• NM_182914.3:c.2409C>A

Your query was ambiguous. Multiple possible variants found:

• chr14-63990506-C-A
• chr14-63990506-C-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_182914.3(SYNE2):​c.2409C>A​(p.Ser803Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00579 in 1,613,746 control chromosomes in the GnomAD database, including 485 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (245 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (240 hom.)
• Consequence: SYNE2 NM_182914.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.595
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• autosomal dominant Emery-Dreifuss muscular dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Emery-Dreifuss muscular dystrophy 5, autosomal dominant

  Inheritance: AD, Unknown Classification: LIMITED, NO_KNOWN Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics
• left ventricular noncompaction

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 14-63990506-C-A is Benign according to our data. Variant chr14-63990506-C-A is described in ClinVar as Benign. ClinVar VariationId is 130493.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.595 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182914.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE2	NM_182914.3	MANE Select	c.2409C>A	p.Ser803Ser	synonymous	Exon 20 of 116	NP_878918.2
	SYNE2	NM_015180.6		c.2409C>A	p.Ser803Ser	synonymous	Exon 20 of 115	NP_055995.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE2	ENST00000555002.6	TSL:1 MANE Select	c.2409C>A	p.Ser803Ser	synonymous	Exon 20 of 116	ENSP00000450831.2
	SYNE2	ENST00000344113.8	TSL:1	c.2409C>A	p.Ser803Ser	synonymous	Exon 20 of 115	ENSP00000341781.4
	SYNE2	ENST00000358025.7	TSL:5	c.2409C>A	p.Ser803Ser	synonymous	Exon 20 of 116	ENSP00000350719.3

Frequencies

GnomAD3 genomes AF: 0.0300 AC: 4557 AN: 152088 Hom.: 242 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0128

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0215

GnomAD2 exomes AF: 0.00794 AC: 1980 AN: 249460 AF XY: 0.00604

Gnomad AFR exome AF: 0.111

Gnomad AMR exome AF: 0.00608

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000239

Gnomad OTH exome AF: 0.00215

GnomAD4 exome AF: 0.00326 AC: 4768 AN: 1461540 Hom.: 240 Cov.: 31 AF XY: 0.00279 AC XY: 2025 AN XY: 727098

African (AFR) AF: 0.114 AC: 3804 AN: 33460

American (AMR) AF: 0.00617 AC: 276 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.000371 AC: 32 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00387 AC: 22 AN: 5678

European-Non Finnish (NFE) AF: 0.000210 AC: 233 AN: 1111866

Other (OTH) AF: 0.00664 AC: 401 AN: 60372

GnomAD4 genome AF: 0.0300 AC: 4572 AN: 152206 Hom.: 245 Cov.: 32 AF XY: 0.0287 AC XY: 2135 AN XY: 74418

African (AFR) AF: 0.104 AC: 4308 AN: 41508

American (AMR) AF: 0.0128 AC: 195 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 68022

Other (OTH) AF: 0.0213 AC: 45 AN: 2114

Alfa AF: 0.0127 Hom.: 61

Bravo AF: 0.0347

Asia WGS AF: 0.00577 AC: 20 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000415

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Emery-Dreifuss muscular dystrophy 5, autosomal dominant (2)
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	1.4
DANN	Benign	0.61
PhyloP100		-0.59
Mutation Taster		=298/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17101525; hg19: chr14-64457224; COSMIC: COSV100648375;