14-63809094-T-C

Variant names:

• chr14-63809094-T-C
• rs7144584

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The variant allele was found at a frequency of 0.934 in 152,242 control chromosomes in the GnomAD database, including 66,583 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 0.93 (66583 hom., cov: 31)
• Consequence: RPS28P1 intragenic
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63
• Publications: 9 publications found

Genes affected

RPS28P1 (HGNC:23561): (ribosomal protein S28 pseudogene 1)

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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS28P1		n.63809094T>C		intragenic_variant
SYNE2	XM_011536576.3	c.-304-43407T>C		intron_variant	Intron 1 of 116		XP_011534878.1
SYNE2	XM_047431152.1	c.-304-43407T>C		intron_variant	Intron 1 of 116		XP_047287108.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE2	ENST00000674003.1	c.-304-43407T>C		intron_variant	Intron 1 of 23			ENSP00000501132.1

Frequencies

GnomAD3 genomes AF: 0.934 AC: 142133 AN: 152124 Hom.: 66521 Cov.: 31

Gnomad AFR AF: 0.982

Gnomad AMI AF: 0.966

Gnomad AMR AF: 0.930

Gnomad ASJ AF: 0.906

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.932

Gnomad FIN AF: 0.930

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.904

Gnomad OTH AF: 0.924

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

GnomAD4 genome AF: 0.934 AC: 142254 AN: 152242 Hom.: 66583 Cov.: 31 AF XY: 0.936 AC XY: 69706 AN XY: 74442

African (AFR) AF: 0.982 AC: 40791 AN: 41534

American (AMR) AF: 0.930 AC: 14226 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.906 AC: 3143 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5173 AN: 5178

South Asian (SAS) AF: 0.931 AC: 4493 AN: 4826

European-Finnish (FIN) AF: 0.930 AC: 9867 AN: 10606

Middle Eastern (MID) AF: 0.918 AC: 270 AN: 294

European-Non Finnish (NFE) AF: 0.904 AC: 61455 AN: 68014

Other (OTH) AF: 0.926 AC: 1955 AN: 2112

Alfa AF: 0.913 Hom.: 143823

Bravo AF: 0.936

Asia WGS AF: 0.965 AC: 3354 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.65
PhyloP100		-1.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7144584; hg19: chr14-64275812;