chr14-63879472-C-T

Variant names:

• chr14-63879472-C-T
• rs4459477
• NM_182914.3:c.-52+26329C>T

Variant summary

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

The NM_182914.3(SYNE2):​c.-52+26329C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,142 control chromosomes in the GnomAD database, including 1,609 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 0.14 (1609 hom., cov: 32)
• Consequence: SYNE2 NM_182914.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.632
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE2	NM_182914.3	c.-52+26329C>T		intron_variant	Intron 1 of 115	ENST00000555002.6	NP_878918.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE2	ENST00000555002.6	c.-52+26329C>T		intron_variant	Intron 1 of 115	1	NM_182914.3	ENSP00000450831.2

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20989 AN: 152024 Hom.: 1597 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.0648

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.0893

Gnomad EAS AF: 0.0498

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0606

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.138 AC: 21044 AN: 152142 Hom.: 1609 Cov.: 32 AF XY: 0.135 AC XY: 10062 AN XY: 74410

African (AFR) AF: 0.208 AC: 8615 AN: 41498

American (AMR) AF: 0.161 AC: 2461 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0893 AC: 310 AN: 3470

East Asian (EAS) AF: 0.0497 AC: 258 AN: 5188

South Asian (SAS) AF: 0.134 AC: 648 AN: 4824

European-Finnish (FIN) AF: 0.0606 AC: 642 AN: 10600

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7753 AN: 67976

Other (OTH) AF: 0.126 AC: 266 AN: 2108

Alfa AF: 0.116 Hom.: 1859

Bravo AF: 0.148

Asia WGS AF: 0.117 AC: 409 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.41
DANN	Benign	0.48
PhyloP100		-0.63
Mutation Taster		=100/0	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: rs4459477; hg19: chr14-64346190;