dbSNP rs895669: DYM:c.2026-88G>A (chr18-49044292-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001353214.3(DYM):c.2026-88G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0799 in 1,488,718 control chromosomes in the GnomAD database, including 5,190 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.072 ( 436 hom., cov: 33)

Exomes 𝑓: 0.081 ( 4754 hom. )

Consequence

DYM
NM_001353214.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.202

Publications

0 publications found

Variant links:

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 links:

DYM-AS1 (HGNC:37046): (DYM antisense RNA 1)

DYM-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 18-49044292-C-T is Benign according to our data. Variant chr18-49044292-C-T is described in ClinVar as Benign. ClinVar VariationId is 1265453.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0859 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DYM	NM_001353214.3	MANE Select	c.2026-88G>A	intron	N/A	NP_001340143.1	A0A6Q8PF81
DYM	NM_001374428.1		c.2026-88G>A	intron	N/A	NP_001361357.1	A0A6Q8PF81
DYM	NM_001353212.3		c.2023-88G>A	intron	N/A	NP_001340141.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DYM	ENST00000675505.1	MANE Select	c.2026-88G>A	intron	N/A	ENSP00000501694.1	A0A6Q8PF81
DYM	ENST00000269445.10	TSL:1	c.1861-88G>A	intron	N/A	ENSP00000269445.6	Q7RTS9-1
DYM	ENST00000919568.1		c.1861-88G>A	intron	N/A	ENSP00000589627.1

Frequencies

GnomAD3 genomes

AF:

0.0723

AC:

10995

AN:

152036

Hom.:

435

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0586

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.0750

Gnomad ASJ

AF:

0.0871

Gnomad EAS

AF:

0.00308

Gnomad SAS

AF:

0.0657

Gnomad FIN

AF:

0.0519

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.0878

Gnomad OTH

AF:

0.0929

GnomAD4 exome

AF:

0.0808

AC:

107943

AN:

1336564

Hom.:

4754

AF XY:

0.0808

AC XY:

54216

AN XY:

670976

show subpopulations

African (AFR)

AF:

0.0609

AC:

1884

AN:

30946

American (AMR)

AF:

0.0547

AC:

2425

AN:

44340

Ashkenazi Jewish (ASJ)

AF:

0.0819

AC:

2082

AN:

25420

East Asian (EAS)

AF:

0.00108

AC:

AN:

38910

South Asian (SAS)

AF:

0.0705

AC:

5869

AN:

83296

European-Finnish (FIN)

AF:

0.0488

AC:

2155

AN:

44162

Middle Eastern (MID)

AF:

0.103

AC:

551

AN:

5354

European-Non Finnish (NFE)

AF:

0.0877

AC:

88367

AN:

1007808

Other (OTH)

AF:

0.0811

AC:

4568

AN:

56328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

5065

10130

15194

20259

25324

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3070

6140

9210

12280

15350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0723

AC:

10997

AN:

152154

Hom.:

436

Cov.:

AF XY:

0.0696

AC XY:

5175

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.0586

AC:

2430

AN:

41494

American (AMR)

AF:

0.0749

AC:

1146

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0871

AC:

302

AN:

3468

East Asian (EAS)

AF:

0.00309

AC:

AN:

5178

South Asian (SAS)

AF:

0.0651

AC:

314

AN:

4820

European-Finnish (FIN)

AF:

0.0519

AC:

550

AN:

10590

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0878

AC:

5968

AN:

67990

Other (OTH)

AF:

0.0919

AC:

194

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

540

1080

1621

2161

2701

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

122

244

366

488

610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0824

Hom.:

Bravo

AF:

0.0726

Asia WGS

AF:

0.0360

AC:

124

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.84

(source)

DANN

Benign

0.43

PhyloP100

-0.20

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over