18-49044292-C-T

Position:

• chr18-49044292-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001353214.3(DYM):​c.2026-88G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0799 in 1,488,718 control chromosomes in the GnomAD database, including 5,190 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.072 (436 hom., cov: 33)
  • Exomes 𝑓: 0.081 (4754 hom.)
• Consequence: DYM NM_001353214.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.202

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 18-49044292-C-T is Benign according to our data. Variant chr18-49044292-C-T is described in ClinVar as [Benign]. Clinvar id is 1265453.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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.2026-88G>A		intron_variant		ENST00000675505.1	NP_001340143.1
DYM-AS1	NR_148999.1	n.313-3836C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYM	ENST00000675505.1	c.2026-88G>A		intron_variant			NM_001353214.3	ENSP00000501694
DYM-AS1	ENST00000584252.1	n.313-3836C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0723 AC: 10995 AN: 152036 Hom.: 435 Cov.: 33

Gnomad AFR AF: 0.0586

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0750

Gnomad ASJ AF: 0.0871

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0657

Gnomad FIN AF: 0.0519

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.0878

Gnomad OTH AF: 0.0929

GnomAD4 exome AF: 0.0808 AC: 107943 AN: 1336564 Hom.: 4754 AF XY: 0.0808 AC XY: 54216 AN XY: 670976

Gnomad4 AFR exome AF: 0.0609

Gnomad4 AMR exome AF: 0.0547

Gnomad4 ASJ exome AF: 0.0819

Gnomad4 EAS exome AF: 0.00108

Gnomad4 SAS exome AF: 0.0705

Gnomad4 FIN exome AF: 0.0488

Gnomad4 NFE exome AF: 0.0877

Gnomad4 OTH exome AF: 0.0811

GnomAD4 genome AF: 0.0723 AC: 10997 AN: 152154 Hom.: 436 Cov.: 33 AF XY: 0.0696 AC XY: 5175 AN XY: 74392

Gnomad4 AFR AF: 0.0586

Gnomad4 AMR AF: 0.0749

Gnomad4 ASJ AF: 0.0871

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.0651

Gnomad4 FIN AF: 0.0519

Gnomad4 NFE AF: 0.0878

Gnomad4 OTH AF: 0.0919

Alfa AF: 0.0835 Hom.: 61

Bravo AF: 0.0726

Asia WGS AF: 0.0360 AC: 124 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.84
DANN	Benign	0.43

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: rs895669; hg19: chr18-46570662;