rs7506861

Variant names:

• chr18-49359073-A-G
• rs7506861
• NM_001353214.3:c.494+4088T>C

Your query was ambiguous. Multiple possible variants found:

• chr18-49359073-A-G
• chr18-49359073-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001353214.3(DYM):​c.494+4088T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 151,874 control chromosomes in the GnomAD database, including 23,199 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.53 (23199 hom., cov: 31)
• Consequence: DYM NM_001353214.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115
• 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 Gene-Disease associations (from GenCC):

• Dyggve-Melchior-Clausen disease

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Orphanet
• Smith-McCort dysplasia 1

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• Smith-McCort dysplasia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYM	NM_001353214.3	c.494+4088T>C		intron_variant	Intron 6 of 17	ENST00000675505.1	NP_001340143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYM	ENST00000675505.1	c.494+4088T>C		intron_variant	Intron 6 of 17		NM_001353214.3	ENSP00000501694.1

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79852 AN: 151754 Hom.: 23188 Cov.: 31

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.740

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.557

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.526 AC: 79891 AN: 151874 Hom.: 23199 Cov.: 31 AF XY: 0.526 AC XY: 38998 AN XY: 74194

African (AFR) AF: 0.262 AC: 10855 AN: 41412

American (AMR) AF: 0.616 AC: 9394 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 1891 AN: 3468

East Asian (EAS) AF: 0.421 AC: 2164 AN: 5146

South Asian (SAS) AF: 0.553 AC: 2660 AN: 4808

European-Finnish (FIN) AF: 0.607 AC: 6399 AN: 10534

Middle Eastern (MID) AF: 0.521 AC: 152 AN: 292

European-Non Finnish (NFE) AF: 0.655 AC: 44529 AN: 67934

Other (OTH) AF: 0.557 AC: 1175 AN: 2110

Alfa AF: 0.517 Hom.: 4224

Bravo AF: 0.512

Asia WGS AF: 0.460 AC: 1600 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	10
DANN	Benign	0.59
PhyloP100		0.12
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: rs7506861; hg19: chr18-46885443;