18-49053600-C-T

Variant names:

• chr18-49053600-C-T
• rs357894
• NM_001353214.3:c.2026-9396G>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.2026-9396G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 151,978 control chromosomes in the GnomAD database, including 24,641 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 0.56 (24641 hom., cov: 32)
• Consequence: DYM NM_001353214.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.423
• Publications: 12 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYM	NM_001353214.3	c.2026-9396G>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.2026-9396G>A		intron_variant	Intron 17 of 17		NM_001353214.3	ENSP00000501694.1
DYM	ENST00000269445.10	c.1861-9396G>A		intron_variant	Intron 16 of 16	1		ENSP00000269445.6
DYM	ENST00000442713.6	c.1291-9396G>A		intron_variant	Intron 11 of 11	2		ENSP00000395942.2
DYM	ENST00000577734.1	c.186-9396G>A		intron_variant	Intron 2 of 2	3		ENSP00000464163.1

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85611 AN: 151860 Hom.: 24619 Cov.: 32

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.604

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

GnomAD4 genome AF: 0.564 AC: 85683 AN: 151978 Hom.: 24641 Cov.: 32 AF XY: 0.565 AC XY: 41942 AN XY: 74252

African (AFR) AF: 0.479 AC: 19837 AN: 41412

American (AMR) AF: 0.667 AC: 10194 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1952 AN: 3466

East Asian (EAS) AF: 0.326 AC: 1683 AN: 5164

South Asian (SAS) AF: 0.512 AC: 2464 AN: 4814

European-Finnish (FIN) AF: 0.612 AC: 6464 AN: 10564

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.606 AC: 41218 AN: 67966

Other (OTH) AF: 0.597 AC: 1262 AN: 2114

Alfa AF: 0.590 Hom.: 70033

Bravo AF: 0.564

Asia WGS AF: 0.425 AC: 1482 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.5
DANN	Benign	0.53
PhyloP100		-0.42
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: rs357894; hg19: chr18-46579970;