18-49061284-G-A

Variant names:

• chr18-49061284-G-A
• rs1787200
• NM_001353214.3:c.2026-17080C>T

Variant summary

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

The NM_001353214.3(DYM):​c.2026-17080C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.713 in 151,960 control chromosomes in the GnomAD database, including 42,408 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 0.71 (42408 hom., cov: 30)
• Consequence: DYM NM_001353214.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.562
• Publications: 19 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.876 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYM	NM_001353214.3	MANE Select	c.2026-17080C>T		intron	N/A	NP_001340143.1
	DYM	NM_001374428.1		c.2026-17080C>T		intron	N/A	NP_001361357.1
	DYM	NM_001353212.3		c.2023-17080C>T		intron	N/A	NP_001340141.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYM	ENST00000675505.1	MANE Select	c.2026-17080C>T		intron	N/A	ENSP00000501694.1
	DYM	ENST00000269445.10	TSL:1	c.1861-17080C>T		intron	N/A	ENSP00000269445.6
	DYM	ENST00000442713.6	TSL:2	c.1291-17080C>T		intron	N/A	ENSP00000395942.2

Frequencies

GnomAD3 genomes AF: 0.713 AC: 108335 AN: 151842 Hom.: 42384 Cov.: 30

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.933

Gnomad AMR AF: 0.811

Gnomad ASJ AF: 0.874

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.712

Gnomad FIN AF: 0.813

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.882

Gnomad OTH AF: 0.775

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

GnomAD4 genome AF: 0.713 AC: 108389 AN: 151960 Hom.: 42408 Cov.: 30 AF XY: 0.711 AC XY: 52809 AN XY: 74258

African (AFR) AF: 0.365 AC: 15097 AN: 41392

American (AMR) AF: 0.811 AC: 12398 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.874 AC: 3032 AN: 3470

East Asian (EAS) AF: 0.621 AC: 3194 AN: 5144

South Asian (SAS) AF: 0.713 AC: 3426 AN: 4804

European-Finnish (FIN) AF: 0.813 AC: 8576 AN: 10550

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.882 AC: 59947 AN: 68002

Other (OTH) AF: 0.777 AC: 1641 AN: 2112

Alfa AF: 0.836 Hom.: 245576

Bravo AF: 0.697

Asia WGS AF: 0.661 AC: 2300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.7
DANN	Benign	0.59
PhyloP100		-0.56
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: rs1787200; hg19: chr18-46587654; COSMIC: COSV53992569;