rs1959033

Positions:

• chr14-63868868-G-A

Variant summary

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

The NM_182914.3(SYNE2):​c.-52+15725G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0557 in 152,188 control chromosomes in the GnomAD database, including 259 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 0.056 (259 hom., cov: 31)
• Consequence: SYNE2 NM_182914.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.442

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=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE2	NM_182914.3	c.-52+15725G>A		intron_variant		ENST00000555002.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE2	ENST00000555002.6	c.-52+15725G>A		intron_variant		1	NM_182914.3	P4

Frequencies

GnomAD3 genomes AF: 0.0558 AC: 8481 AN: 152070 Hom.: 260 Cov.: 31

Gnomad AFR AF: 0.0404

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.0566

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.0732

Gnomad SAS AF: 0.0651

Gnomad FIN AF: 0.0640

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0582

Gnomad OTH AF: 0.0622

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

GnomAD4 genome AF: 0.0557 AC: 8477 AN: 152188 Hom.: 259 Cov.: 31 AF XY: 0.0572 AC XY: 4258 AN XY: 74400

Gnomad4 AFR AF: 0.0404

Gnomad4 AMR AF: 0.0565

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.0730

Gnomad4 SAS AF: 0.0649

Gnomad4 FIN AF: 0.0640

Gnomad4 NFE AF: 0.0582

Gnomad4 OTH AF: 0.0611

Alfa AF: 0.0610 Hom.: 167

Bravo AF: 0.0560

Asia WGS AF: 0.0540 AC: 187 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	7.6
DANN	Benign	0.78

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: rs1959033; hg19: chr14-64335586;