rs10140978

Variant names:

• chr14-64061353-G-A
• rs10140978
• NM_182914.3:c.10068-1398G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-64061353-G-A
• chr14-64061353-G-C
• chr14-64061353-G-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.10068-1398G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.894 in 152,242 control chromosomes in the GnomAD database, including 61,051 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 0.89 (61051 hom., cov: 33)
• Consequence: SYNE2 NM_182914.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.301
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.935 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE2	NM_182914.3	MANE Select	c.10068-1398G>A		intron	N/A	NP_878918.2
	SYNE2	NM_015180.6		c.10068-1398G>A		intron	N/A	NP_055995.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE2	ENST00000555002.6	TSL:1 MANE Select	c.10068-1398G>A		intron	N/A	ENSP00000450831.2
	SYNE2	ENST00000344113.8	TSL:1	c.10068-1398G>A		intron	N/A	ENSP00000341781.4
	SYNE2	ENST00000358025.7	TSL:5	c.10068-1398G>A		intron	N/A	ENSP00000350719.3

Frequencies

GnomAD3 genomes AF: 0.894 AC: 135946 AN: 152124 Hom.: 61005 Cov.: 33

Gnomad AFR AF: 0.817

Gnomad AMI AF: 0.995

Gnomad AMR AF: 0.911

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.844

Gnomad SAS AF: 0.800

Gnomad FIN AF: 0.944

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.941

Gnomad OTH AF: 0.889

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

GnomAD4 genome AF: 0.894 AC: 136050 AN: 152242 Hom.: 61051 Cov.: 33 AF XY: 0.892 AC XY: 66431 AN XY: 74444

African (AFR) AF: 0.817 AC: 33897 AN: 41506

American (AMR) AF: 0.912 AC: 13951 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.831 AC: 2884 AN: 3472

East Asian (EAS) AF: 0.844 AC: 4369 AN: 5178

South Asian (SAS) AF: 0.801 AC: 3858 AN: 4818

European-Finnish (FIN) AF: 0.944 AC: 10021 AN: 10618

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.941 AC: 64033 AN: 68028

Other (OTH) AF: 0.887 AC: 1873 AN: 2112

Alfa AF: 0.918 Hom.: 36529

Bravo AF: 0.891

Asia WGS AF: 0.820 AC: 2850 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.1
DANN	Benign	0.68
PhyloP100		0.30
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: rs10140978; hg19: chr14-64528071;