18-49044502-C-G

Variant names:

• chr18-49044502-C-G
• rs895670
• NM_001353214.3:c.2026-298G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001353214.3(DYM):​c.2026-298G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0737 in 152,328 control chromosomes in the GnomAD database, including 449 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.074 (449 hom., cov: 33)
• Consequence: DYM NM_001353214.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.515
• Publications: 1 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-AS1 (HGNC:37046): (DYM antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 18-49044502-C-G is Benign according to our data. Variant chr18-49044502-C-G is described in ClinVar as [Benign]. Clinvar id is 1276579.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYM	NM_001353214.3	c.2026-298G>C		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.2026-298G>C		intron_variant	Intron 17 of 17		NM_001353214.3	ENSP00000501694.1

Frequencies

GnomAD3 genomes AF: 0.0738 AC: 11229 AN: 152210 Hom.: 448 Cov.: 33

Gnomad AFR AF: 0.0636

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0756

Gnomad ASJ AF: 0.0873

Gnomad EAS AF: 0.00288

Gnomad SAS AF: 0.0660

Gnomad FIN AF: 0.0523

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.0877

Gnomad OTH AF: 0.0933

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

GnomAD4 genome AF: 0.0737 AC: 11231 AN: 152328 Hom.: 449 Cov.: 33 AF XY: 0.0710 AC XY: 5288 AN XY: 74496

African (AFR) AF: 0.0636 AC: 2643 AN: 41562

American (AMR) AF: 0.0755 AC: 1156 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0873 AC: 303 AN: 3472

East Asian (EAS) AF: 0.00289 AC: 15 AN: 5188

South Asian (SAS) AF: 0.0655 AC: 316 AN: 4828

European-Finnish (FIN) AF: 0.0523 AC: 556 AN: 10624

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.0878 AC: 5970 AN: 68028

Other (OTH) AF: 0.0923 AC: 195 AN: 2112

Alfa AF: 0.0844 Hom.: 61

Bravo AF: 0.0744

Asia WGS AF: 0.0350 AC: 121 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.24
DANN	Benign	0.40
PhyloP100		-0.52
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: rs895670; hg19: chr18-46570872;