rs7506861

Positions:

• chr18-49359073-A-G
• chr18-49359073-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.494+4088T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 151,874 control chromosomes in the GnomAD database, including 23,199 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 0.53 (23199 hom., cov: 31)
• Consequence: DYM NM_001353214.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DYM	NM_001353214.3	c.494+4088T>C		intron_variant		ENST00000675505.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYM	ENST00000675505.1	c.494+4088T>C		intron_variant			NM_001353214.3

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79852 AN: 151754 Hom.: 23188 Cov.: 31

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.740

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.526 AC: 79891 AN: 151874 Hom.: 23199 Cov.: 31 AF XY: 0.526 AC XY: 38998 AN XY: 74194

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.616

Gnomad4 ASJ AF: 0.545

Gnomad4 EAS AF: 0.421

Gnomad4 SAS AF: 0.553

Gnomad4 FIN AF: 0.607

Gnomad4 NFE AF: 0.655

Gnomad4 OTH AF: 0.557

Alfa AF: 0.524 Hom.: 4197

Bravo AF: 0.512

Asia WGS AF: 0.460 AC: 1600 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	10
DANN	Benign	0.59

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: rs7506861; hg19: chr18-46885443;