rs833497

Variant names:

• chr18-49081890-T-C
• rs833497
• NM_001353214.3:c.2025+15512A>G

Variant summary

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

The NM_001353214.3(DYM):​c.2025+15512A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,184 control chromosomes in the GnomAD database, including 2,777 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 0.17 (2777 hom., cov: 32)
• Consequence: DYM NM_001353214.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.240
• Publications: 5 publications found

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]

DYM Gene-Disease associations (from GenCC):

• Dyggve-Melchior-Clausen disease

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P
• Smith-McCort dysplasia 1

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• Smith-McCort dysplasia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353214.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYM	NM_001353214.3	MANE Select	c.2025+15512A>G		intron	N/A	NP_001340143.1	A0A6Q8PF81
	DYM	NM_001374428.1		c.2025+15512A>G		intron	N/A	NP_001361357.1	A0A6Q8PF81
	DYM	NM_001353212.3		c.2022+15512A>G		intron	N/A	NP_001340141.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYM	ENST00000675505.1	MANE Select	c.2025+15512A>G		intron	N/A	ENSP00000501694.1	A0A6Q8PF81
	DYM	ENST00000269445.10	TSL:1	c.1860+15512A>G		intron	N/A	ENSP00000269445.6	Q7RTS9-1
	DYM	ENST00000919568.1		c.1860+15512A>G		intron	N/A	ENSP00000589627.1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25335 AN: 152066 Hom.: 2762 Cov.: 32

Gnomad AFR AF: 0.0700

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.0617

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.167 AC: 25375 AN: 152184 Hom.: 2777 Cov.: 32 AF XY: 0.175 AC XY: 12988 AN XY: 74386

African (AFR) AF: 0.0700 AC: 2910 AN: 41550

American (AMR) AF: 0.325 AC: 4977 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0617 AC: 214 AN: 3470

East Asian (EAS) AF: 0.336 AC: 1734 AN: 5158

South Asian (SAS) AF: 0.195 AC: 940 AN: 4826

European-Finnish (FIN) AF: 0.251 AC: 2652 AN: 10568

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11445 AN: 68002

Other (OTH) AF: 0.159 AC: 335 AN: 2108

Alfa AF: 0.162 Hom.: 3861

Bravo AF: 0.171

Asia WGS AF: 0.247 AC: 859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.9
DANN	Benign	0.61
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs833497; hg19: chr18-46608260;