NM_182914.3:c.7162G>T

Variant names:

• chr14-64031298-G-T
• rs200842904
• NM_182914.3:c.7162G>T

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_182914.3(SYNE2):​c.7162G>T​(p.Glu2388*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SYNE2 NM_182914.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320
• 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: Pathogenic. The variant received 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE2	NM_182914.3	MANE Select	c.7162G>T	p.Glu2388*	stop_gained	Exon 45 of 116	NP_878918.2
	SYNE2	NM_015180.6		c.7162G>T	p.Glu2388*	stop_gained	Exon 45 of 115	NP_055995.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE2	ENST00000555002.6	TSL:1 MANE Select	c.7162G>T	p.Glu2388*	stop_gained	Exon 45 of 116	ENSP00000450831.2
	SYNE2	ENST00000344113.8	TSL:1	c.7162G>T	p.Glu2388*	stop_gained	Exon 45 of 115	ENSP00000341781.4
	SYNE2	ENST00000358025.7	TSL:5	c.7162G>T	p.Glu2388*	stop_gained	Exon 45 of 116	ENSP00000350719.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 64

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	36
DANN	Uncertain	0.99
Eigen	Uncertain	0.29
Eigen_PC	Benign	0.029
FATHMM_MKL	Benign	0.12	N
PhyloP100		0.032
Vest4		0.82
GERP RS		4.2
Mutation Taster		=50/150	disease causing (fs/PTC)

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: rs200842904; hg19: chr14-64498016;