rs10775489

chr18-49140929-G-A

Variant summary

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

The NM_001353214.3(DYM):c.1729-22003C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,082 control chromosomes in the GnomAD database, including 2,138 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 0.15 (2138 hom., cov: 32)
• Consequence: DYM NM_001353214.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DYM	NM_001353214.3	c.1729-22003C>T		intron_variant		ENST00000675505.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYM	ENST00000675505.1	c.1729-22003C>T		intron_variant			NM_001353214.3
DYM	ENST00000269445.10	c.1564-22003C>T		intron_variant		1		P1
DYM	ENST00000442713.6	c.994-22003C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23381 AN: 151962 Hom.: 2128 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.154 AC: 23415 AN: 152082 Hom.: 2138 Cov.: 32 AF XY: 0.158 AC XY: 11781 AN XY: 74356

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.146

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.151

Alfa AF: 0.150 Hom.: 2387

Bravo AF: 0.153

Asia WGS AF: 0.329 AC: 1140 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.19
Dann	Benign	0.36

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: rs10775489; hg19: chr18-46667299;