18-49044334-A-G

Variant names:

• chr18-49044334-A-G
• rs45588531
• NM_001353214.3:c.2026-130T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.629
• Publications: 2 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 -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
DYM	NM_001353214.3	c.2026-130T>C		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.2026-130T>C		intron_variant	Intron 17 of 17		NM_001353214.3	ENSP00000501694.1

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

African (AFR) AF: 0.256 AC: 5178 AN: 20252

American (AMR) AF: 0.164 AC: 6601 AN: 40300

Ashkenazi Jewish (ASJ) AF: 0.0757 AC: 1632 AN: 21558

East Asian (EAS) AF: 0.324 AC: 11604 AN: 35812

South Asian (SAS) AF: 0.118 AC: 8390 AN: 70824

European-Finnish (FIN) AF: 0.149 AC: 5767 AN: 38692

Middle Eastern (MID) AF: 0.0972 AC: 363 AN: 3736

European-Non Finnish (NFE) AF: 0.0687 AC: 35755 AN: 520160

Other (OTH) AF: 0.104 AC: 3996 AN: 38378

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

African (AFR) AF: 0.248 AC: 10286 AN: 41488

American (AMR) AF: 0.119 AC: 1818 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0674 AC: 234 AN: 3472

East Asian (EAS) AF: 0.299 AC: 1548 AN: 5178

South Asian (SAS) AF: 0.115 AC: 556 AN: 4830

European-Finnish (FIN) AF: 0.163 AC: 1722 AN: 10586

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0731 AC: 4972 AN: 67998

Other (OTH) AF: 0.107 AC: 226 AN: 2114

Alfa AF: 0.136 Hom.: 289

Bravo AF: 0.144

Asia WGS AF: 0.193 AC: 669 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.41
PhyloP100		-0.63
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: rs45588531; hg19: chr18-46570704; COSMIC: COSV53979855;