14-63848602-G-T

Variant names:

• chr14-63848602-G-T
• rs11158515
• ENST00000674003.1:c.-304-3899G>T

Variant summary

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

The ENST00000674003.1(SYNE2):​c.-304-3899G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 152,026 control chromosomes in the GnomAD database, including 15,457 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 0.42 (15457 hom., cov: 32)
• Consequence: SYNE2 ENST00000674003.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.281
• Publications: 2 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

Y_RNA (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.549 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE2	ENST00000674003.1		c.-304-3899G>T		intron	N/A	ENSP00000501132.1
	Y_RNA	ENST00000365312.1	TSL:6	n.-240C>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64497 AN: 151908 Hom.: 15444 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.424 AC: 64531 AN: 152026 Hom.: 15457 Cov.: 32 AF XY: 0.432 AC XY: 32081 AN XY: 74304

African (AFR) AF: 0.194 AC: 8062 AN: 41464

American (AMR) AF: 0.468 AC: 7137 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 1707 AN: 3470

East Asian (EAS) AF: 0.364 AC: 1884 AN: 5170

South Asian (SAS) AF: 0.567 AC: 2733 AN: 4820

European-Finnish (FIN) AF: 0.602 AC: 6345 AN: 10544

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.517 AC: 35177 AN: 67984

Other (OTH) AF: 0.458 AC: 965 AN: 2108

Alfa AF: 0.477 Hom.: 8555

Bravo AF: 0.399

Asia WGS AF: 0.452 AC: 1577 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.6
DANN	Benign	0.63
PhyloP100		-0.28

Splicing

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

Other links and lift over

dbSNP: rs11158515; hg19: chr14-64315320;