18-49433130-G-C

Variant names:

• chr18-49433130-G-C
• rs9967417
• NM_001353214.3:c.-53-2683C>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.-53-2683C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 152,026 control chromosomes in the GnomAD database, including 36,489 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 0.68 (36489 hom., cov: 31)
• Consequence: DYM NM_001353214.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.873
• Publications: 42 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Orphanet
• 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

ENSG00000263895 (HGNC:):

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 = 0.97 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYM	NM_001353214.3	c.-53-2683C>G		intron_variant	Intron 1 of 17	ENST00000675505.1	NP_001340143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYM	ENST00000675505.1	c.-53-2683C>G		intron_variant	Intron 1 of 17		NM_001353214.3	ENSP00000501694.1

Frequencies

GnomAD3 genomes AF: 0.682 AC: 103611 AN: 151908 Hom.: 36433 Cov.: 31

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.720

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.992

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.737

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.636

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

GnomAD4 genome AF: 0.682 AC: 103731 AN: 152026 Hom.: 36489 Cov.: 31 AF XY: 0.692 AC XY: 51446 AN XY: 74314

African (AFR) AF: 0.811 AC: 33619 AN: 41460

American (AMR) AF: 0.720 AC: 11006 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1854 AN: 3468

East Asian (EAS) AF: 0.992 AC: 5128 AN: 5168

South Asian (SAS) AF: 0.737 AC: 3550 AN: 4818

European-Finnish (FIN) AF: 0.737 AC: 7789 AN: 10572

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.571 AC: 38773 AN: 67950

Other (OTH) AF: 0.640 AC: 1351 AN: 2110

Alfa AF: 0.580 Hom.: 13085

Bravo AF: 0.691

Asia WGS AF: 0.872 AC: 3030 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	1.3
DANN	Benign	0.63
PhyloP100		-0.87
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: rs9967417; hg19: chr18-46959500;