rs10140978

chr14-64061353-G-Achr14-64061353-G-Cchr14-64061353-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE2	NM_182914.3	c.10068-1398G>A		intron_variant		ENST00000555002.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE2	ENST00000555002.6	c.10068-1398G>A		intron_variant		1	NM_182914.3	P4

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

Gnomad4 AFR AF: 0.817

Gnomad4 AMR AF: 0.912

Gnomad4 ASJ AF: 0.831

Gnomad4 EAS AF: 0.844

Gnomad4 SAS AF: 0.801

Gnomad4 FIN AF: 0.944

Gnomad4 NFE AF: 0.941

Gnomad4 OTH AF: 0.887

Alfa AF: 0.917 Hom.: 33189

Bravo AF: 0.891

Asia WGS AF: 0.820 AC: 2850 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.1
Dann	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs10140978; hg19: chr14-64528071;