18-49460364-C-G

Position:

• chr18-49460364-C-G

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.-54+34G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,176 control chromosomes in the GnomAD database, including 2,945 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2941 hom., cov: 32)
  • Exomes 𝑓: 0.27 (4 hom.)
• Consequence: DYM NM_001353214.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.58

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 18-49460364-C-G is Benign according to our data. Variant chr18-49460364-C-G is described in ClinVar as [Benign]. Clinvar id is 402809.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYM	NM_001353214.3	c.-54+34G>C		intron_variant		ENST00000675505.1	NP_001340143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYM	ENST00000675505.1	c.-54+34G>C		intron_variant			NM_001353214.3	ENSP00000501694

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27177 AN: 152002 Hom.: 2943 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.148

GnomAD4 exome AF: 0.268 AC: 15 AN: 56 Hom.: 4 Cov.: 0 AF XY: 0.200 AC XY: 8 AN XY: 40

Gnomad4 EAS exome AF: 0.750

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.179 AC: 27187 AN: 152120 Hom.: 2941 Cov.: 32 AF XY: 0.187 AC XY: 13889 AN XY: 74370

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.490

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.151

Alfa AF: 0.187 Hom.: 374

Bravo AF: 0.168

Asia WGS AF: 0.405 AC: 1408 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in 1000Genomes: 566/2178= 25.98% -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 09, 2017	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.63

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: rs60901553; hg19: chr18-46986734;