rs60901553

Variant names:

• chr18-49460364-C-G
• rs60901553
• NM_001353214.3:c.-54+34G>C

Your query was ambiguous. Multiple possible variants found:

• chr18-49460364-C-G
• chr18-49460364-C-A

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.-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
• Publications: 5 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: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P
• 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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353214.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYM	NM_001353214.3	MANE Select	c.-54+34G>C		intron	N/A	NP_001340143.1	A0A6Q8PF81
	DYM	NM_001374428.1		c.-312+34G>C		intron	N/A	NP_001361357.1	A0A6Q8PF81
	DYM	NM_001353212.3		c.-54+34G>C		intron	N/A	NP_001340141.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYM	ENST00000675505.1	MANE Select	c.-54+34G>C		intron	N/A	ENSP00000501694.1	A0A6Q8PF81
	DYM	ENST00000269445.10	TSL:1	c.-54+34G>C		intron	N/A	ENSP00000269445.6	Q7RTS9-1
	DYM	ENST00000919568.1		c.-318G>C		5_prime_UTR	Exon 1 of 17	ENSP00000589627.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.750 AC: 3 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 12 AN: 48

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.109 AC: 4520 AN: 41542

American (AMR) AF: 0.172 AC: 2629 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 581 AN: 3468

East Asian (EAS) AF: 0.490 AC: 2506 AN: 5112

South Asian (SAS) AF: 0.322 AC: 1558 AN: 4832

European-Finnish (FIN) AF: 0.255 AC: 2701 AN: 10588

Middle Eastern (MID) AF: 0.151 AC: 44 AN: 292

European-Non Finnish (NFE) AF: 0.179 AC: 12162 AN: 67960

Other (OTH) AF: 0.151 AC: 319 AN: 2112

Alfa AF: 0.187 Hom.: 374

Bravo AF: 0.168

Asia WGS AF: 0.405 AC: 1408 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.63
PhyloP100		-1.6
PromoterAI		-0.038	Neutral
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: rs60901553; hg19: chr18-46986734;