18-49044334-A-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.2026-130T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 941,876 control chromosomes in the GnomAD database, including 7,798 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (2006 hom., cov: 33)
  • Exomes 𝑓: 0.10 (5792 hom.)
• Consequence: DYM NM_001353214.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.629

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=-0.91).
• BP6: Variant 18-49044334-A-G is Benign according to our data. Variant chr18-49044334-A-G is described in ClinVar as [Benign]. Clinvar id is 1222967.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DYM	NM_001353214.3	c.2026-130T>C		intron_variant		ENST00000675505.1
DYM-AS1	NR_148999.1	n.313-3794A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYM	ENST00000675505.1	c.2026-130T>C		intron_variant			NM_001353214.3
DYM-AS1	ENST00000584252.1	n.313-3794A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21393 AN: 152046 Hom.: 1997 Cov.: 33

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.0440

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.0674

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0731

Gnomad OTH AF: 0.108

GnomAD4 exome AF: 0.100 AC: 79286 AN: 789712 Hom.: 5792 AF XY: 0.0997 AC XY: 41585 AN XY: 417152

Gnomad4 AFR exome AF: 0.256

Gnomad4 AMR exome AF: 0.164

Gnomad4 ASJ exome AF: 0.0757

Gnomad4 EAS exome AF: 0.324

Gnomad4 SAS exome AF: 0.118

Gnomad4 FIN exome AF: 0.149

Gnomad4 NFE exome AF: 0.0687

Gnomad4 OTH exome AF: 0.104

GnomAD4 genome AF: 0.141 AC: 21429 AN: 152164 Hom.: 2006 Cov.: 33 AF XY: 0.146 AC XY: 10833 AN XY: 74406

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.0674

Gnomad4 EAS AF: 0.299

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.0731

Gnomad4 OTH AF: 0.107

Alfa AF: 0.131 Hom.: 264

Bravo AF: 0.144

Asia WGS AF: 0.193 AC: 669 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 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.4
Dann	Benign	0.41

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: rs45588531; hg19: chr18-46570704; COSMIC: COSV53979855;