rs8087713

Positions:

• chr18-49150815-A-G
• chr18-49150815-A-T

Variant summary

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

The NM_001353214.3(DYM):​c.1728+12870T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,124 control chromosomes in the GnomAD database, including 2,295 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 0.16 (2295 hom., cov: 32)
• Consequence: DYM NM_001353214.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04

Genes affected

DYM (HGNC:21317): (dymeclin) This gene encodes a protein which regulates Golgi-associated secretory pathways that are essential to endochondral bone formation during early development. This gene is also believed to play a role in early brain development. This gene is widely expressed in embryos and is particularly abundant in chodrocytes and brain tissues. It encodes a peripheral membrane protein which shuttles between the cytosol and Golgi complex. Mutations in this gene are associated with two types of recessive osteochondrodysplasia: Dyggve-Melchior-Clausen (DMC) dysplasia and Smith-McCort (SMC) dysplasia. [provided by RefSeq, Jun 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DYM	NM_001353214.3	c.1728+12870T>C		intron_variant		ENST00000675505.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYM	ENST00000675505.1	c.1728+12870T>C		intron_variant			NM_001353214.3
DYM	ENST00000269445.10	c.1563+12870T>C		intron_variant		1		P1
DYM	ENST00000442713.6	c.993+12870T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24457 AN: 152006 Hom.: 2286 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.161 AC: 24490 AN: 152124 Hom.: 2295 Cov.: 32 AF XY: 0.165 AC XY: 12261 AN XY: 74362

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.390

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.159

Alfa AF: 0.151 Hom.: 940

Bravo AF: 0.161

Asia WGS AF: 0.336 AC: 1167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	15
DANN	Benign	0.74

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: rs8087713; hg19: chr18-46677185;