chr18-49044502-C-G

Position:

• chr18-49044502-C-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
DYM	NM_001353214.3	c.2026-298G>C		intron_variant		ENST00000675505.1	NP_001340143.1
DYM-AS1	NR_148999.1	n.313-3626C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYM	ENST00000675505.1	c.2026-298G>C		intron_variant			NM_001353214.3	ENSP00000501694
DYM-AS1	ENST00000584252.1	n.313-3626C>G		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.0636

Gnomad4 AMR AF: 0.0755

Gnomad4 ASJ AF: 0.0873

Gnomad4 EAS AF: 0.00289

Gnomad4 SAS AF: 0.0655

Gnomad4 FIN AF: 0.0523

Gnomad4 NFE AF: 0.0878

Gnomad4 OTH AF: 0.0923

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.24
DANN	Benign	0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs895670; hg19: chr18-46570872;