18-49057814-C-T

Variant names:

• chr18-49057814-C-T
• rs357897
• NM_001353214.3:c.2026-13610G>A

Variant summary

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

The NM_001353214.3(DYM):​c.2026-13610G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 152,226 control chromosomes in the GnomAD database, including 38,807 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 (38807 hom., cov: 34)
• Consequence: DYM NM_001353214.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.60
• Publications: 7 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYM	NM_001353214.3	c.2026-13610G>A		intron_variant	Intron 17 of 17	ENST00000675505.1	NP_001340143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYM	ENST00000675505.1	c.2026-13610G>A		intron_variant	Intron 17 of 17		NM_001353214.3	ENSP00000501694.1
DYM	ENST00000269445.10	c.1861-13610G>A		intron_variant	Intron 16 of 16	1		ENSP00000269445.6
DYM	ENST00000442713.6	c.1291-13610G>A		intron_variant	Intron 11 of 11	2		ENSP00000395942.2
DYM	ENST00000577734.1	c.186-13610G>A		intron_variant	Intron 2 of 2	3		ENSP00000464163.1

Frequencies

GnomAD3 genomes AF: 0.683 AC: 103964 AN: 152108 Hom.: 38784 Cov.: 34

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.924

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.840

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.785

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.837

Gnomad OTH AF: 0.730

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

GnomAD4 genome AF: 0.683 AC: 104017 AN: 152226 Hom.: 38807 Cov.: 34 AF XY: 0.683 AC XY: 50814 AN XY: 74428

African (AFR) AF: 0.357 AC: 14801 AN: 41492

American (AMR) AF: 0.769 AC: 11777 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.840 AC: 2916 AN: 3472

East Asian (EAS) AF: 0.620 AC: 3214 AN: 5182

South Asian (SAS) AF: 0.716 AC: 3455 AN: 4824

European-Finnish (FIN) AF: 0.785 AC: 8317 AN: 10596

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.837 AC: 56936 AN: 68034

Other (OTH) AF: 0.733 AC: 1547 AN: 2110

Alfa AF: 0.790 Hom.: 63734

Bravo AF: 0.667

Asia WGS AF: 0.660 AC: 2295 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.0050
DANN	Benign	0.43
PhyloP100		-3.6
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: rs357897; hg19: chr18-46584184;