18-49044234-C-T

Variant names:

• chr18-49044234-C-T
• rs75309715
• NM_001353214.3:c.2026-30G>A

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.2026-30G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00477 in 1,613,132 control chromosomes in the GnomAD database, including 239 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0095 (34 hom., cov: 33)
  • Exomes 𝑓: 0.0043 (205 hom.)
• Consequence: DYM NM_001353214.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.106
• 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=-0.79).
• BP6: Variant 18-49044234-C-T is Benign according to our data. Variant chr18-49044234-C-T is described in ClinVar as [Benign]. Clinvar id is 1226923.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYM	NM_001353214.3	c.2026-30G>A		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.2026-30G>A		intron_variant	Intron 17 of 17		NM_001353214.3	ENSP00000501694.1

Frequencies

GnomAD3 genomes AF: 0.00948 AC: 1442 AN: 152158 Hom.: 34 Cov.: 33

Gnomad AFR AF: 0.0257

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0681

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00575

GnomAD2 exomes AF: 0.00926 AC: 2310 AN: 249520 AF XY: 0.0113

Gnomad AFR exome AF: 0.0300

Gnomad AMR exome AF: 0.000724

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000124

Gnomad OTH exome AF: 0.00427

GnomAD4 exome AF: 0.00429 AC: 6261 AN: 1460856 Hom.: 205 Cov.: 30 AF XY: 0.00575 AC XY: 4180 AN XY: 726766

African (AFR) AF: 0.0286 AC: 958 AN: 33468

American (AMR) AF: 0.000827 AC: 37 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.000680 AC: 27 AN: 39692

South Asian (SAS) AF: 0.0556 AC: 4791 AN: 86212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52878

Middle Eastern (MID) AF: 0.00417 AC: 24 AN: 5756

European-Non Finnish (NFE) AF: 0.0000684 AC: 76 AN: 1111634

Other (OTH) AF: 0.00576 AC: 348 AN: 60366

GnomAD4 genome AF: 0.00946 AC: 1440 AN: 152276 Hom.: 34 Cov.: 33 AF XY: 0.0102 AC XY: 759 AN XY: 74460

African (AFR) AF: 0.0257 AC: 1069 AN: 41558

American (AMR) AF: 0.00144 AC: 22 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5186

South Asian (SAS) AF: 0.0670 AC: 323 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68010

Other (OTH) AF: 0.00569 AC: 12 AN: 2108

Alfa AF: 0.00384 Hom.: 6

Bravo AF: 0.00876

Asia WGS AF: 0.0400 AC: 142 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 11, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.74
PhyloP100		-0.11
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: rs75309715; hg19: chr18-46570604;