rs12889954

Positions:

• chr14-63920750-T-C
• chr14-63920750-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000555002.6(SYNE2):​c.79+11523T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 151,280 control chromosomes in the GnomAD database, including 5,215 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 0.23 (5215 hom., cov: 29)
• Consequence: SYNE2 ENST00000555002.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNE2	NM_182914.3	c.79+11523T>C		intron_variant		ENST00000555002.6	NP_878918.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNE2	ENST00000555002.6	c.79+11523T>C		intron_variant		1	NM_182914.3	ENSP00000450831	P4

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35427 AN: 151162 Hom.: 5208 Cov.: 29

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.234 AC: 35463 AN: 151280 Hom.: 5215 Cov.: 29 AF XY: 0.232 AC XY: 17139 AN XY: 73868

Gnomad4 AFR AF: 0.422

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.214

Alfa AF: 0.176 Hom.: 2534

Bravo AF: 0.251

Asia WGS AF: 0.203 AC: 707 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.4
DANN	Benign	0.77

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: rs12889954; hg19: chr14-64387468;