rs17101394

Variant names:

• chr14-63765668-G-A
• rs17101394
• ENST00000674003.1:c.-305+3682G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-63765668-G-A
• chr14-63765668-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000674003.1(SYNE2):​c.-305+3682G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 151,940 control chromosomes in the GnomAD database, including 2,223 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2223 hom., cov: 32)
• Consequence: SYNE2 ENST00000674003.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 17 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
• left ventricular noncompaction

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• Emery-Dreifuss muscular dystrophy 5, autosomal dominant

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000674003.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE2	ENST00000674003.1		c.-305+3682G>A		intron	N/A	ENSP00000501132.1	A0A669KB61

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25498 AN: 151822 Hom.: 2217 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.173

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.168 AC: 25534 AN: 151940 Hom.: 2223 Cov.: 32 AF XY: 0.167 AC XY: 12384 AN XY: 74272

African (AFR) AF: 0.186 AC: 7707 AN: 41448

American (AMR) AF: 0.204 AC: 3108 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 723 AN: 3464

East Asian (EAS) AF: 0.102 AC: 529 AN: 5168

South Asian (SAS) AF: 0.132 AC: 636 AN: 4826

European-Finnish (FIN) AF: 0.118 AC: 1247 AN: 10556

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.163 AC: 11068 AN: 67922

Other (OTH) AF: 0.171 AC: 361 AN: 2108

Alfa AF: 0.163 Hom.: 5924

Bravo AF: 0.176

Asia WGS AF: 0.124 AC: 431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.31
DANN	Benign	0.51
PhyloP100		-1.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17101394; hg19: chr14-64232386;