NM_001353214.3:c.1728+12870T>C

Variant names:

• chr18-49150815-A-G
• rs8087713
• NM_001353214.3:c.1728+12870T>C

Variant summary

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

The NM_001353214.3(DYM):​c.1728+12870T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,124 control chromosomes in the GnomAD database, including 2,295 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 0.16 (2295 hom., cov: 32)
• Consequence: DYM NM_001353214.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04
• Publications: 4 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.376 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.1728+12870T>C		intron	N/A	NP_001340143.1	A0A6Q8PF81
	DYM	NM_001374428.1		c.1728+12870T>C		intron	N/A	NP_001361357.1	A0A6Q8PF81
	DYM	NM_001353212.3		c.1725+12870T>C		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.1728+12870T>C		intron	N/A	ENSP00000501694.1	A0A6Q8PF81
	DYM	ENST00000269445.10	TSL:1	c.1563+12870T>C		intron	N/A	ENSP00000269445.6	Q7RTS9-1
	DYM	ENST00000919568.1		c.1563+12870T>C		intron	N/A	ENSP00000589627.1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24457 AN: 152006 Hom.: 2286 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.161 AC: 24490 AN: 152124 Hom.: 2295 Cov.: 32 AF XY: 0.165 AC XY: 12261 AN XY: 74362

African (AFR) AF: 0.105 AC: 4344 AN: 41520

American (AMR) AF: 0.190 AC: 2902 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 606 AN: 3468

East Asian (EAS) AF: 0.390 AC: 2015 AN: 5168

South Asian (SAS) AF: 0.253 AC: 1218 AN: 4816

European-Finnish (FIN) AF: 0.163 AC: 1726 AN: 10562

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.163 AC: 11067 AN: 67996

Other (OTH) AF: 0.159 AC: 335 AN: 2112

Alfa AF: 0.151 Hom.: 1055

Bravo AF: 0.161

Asia WGS AF: 0.336 AC: 1167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	15
DANN	Benign	0.74
PhyloP100		2.0
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: rs8087713; hg19: chr18-46677185;