rs2650907

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_199355.4(ADAMTS18):c.1322+8C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 1,610,402 control chromosomes in the GnomAD database, including 263,511 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 21928 hom., cov: 32)

Exomes 𝑓: 0.57 ( 241583 hom. )

Consequence

ADAMTS18
NM_199355.4 splice_region, intron

Scores

Splicing: ADA: 0.00003301

Clinical Significance

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

Conservation

PhyloP100: 0.229

Publications

16 publications found

Variant links:

Genes affected

ADAMTS18 (HGNC:17110): (ADAM metallopeptidase with thrombospondin type 1 motif 18) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. ADAMTS family members share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The encoded preproprotein is proteolytically processed to generate the mature protein, which may regulate hemostatic balance and function as a tumor suppressor. Mutations in this gene may be associated with microcornea, myopic chorioretinal atrophy, and telecanthus (MMCAT) and cone-rod dystrophy in human patients. [provided by RefSeq, May 2016]

ADAMTS18 Gene-Disease associations (from GenCC):

microcornea-myopic chorioretinal atrophy
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, G2P
inherited retinal dystrophy
Inheritance: AR Classification: LIMITED Submitted by: Franklin by Genoox

ADAMTS18 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=-0.82).

BP6

Variant 16-77359310-G-C is Benign according to our data. Variant chr16-77359310-G-C is described in ClinVar as Benign. ClinVar VariationId is 1168654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199355.4. 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
	ADAMTS18	NM_199355.4	MANE Select	c.1322+8C>G		splice_region intron	N/A	NP_955387.1	Q8TE60-1
	ADAMTS18	NM_001326358.2		c.806+8C>G		splice_region intron	N/A	NP_001313287.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS18	ENST00000282849.10	TSL:1 MANE Select	c.1322+8C>G		splice_region intron	N/A	ENSP00000282849.5	Q8TE60-1
	ADAMTS18	ENST00000449265.2	TSL:2	n.*341+8C>G		splice_region intron	N/A	ENSP00000392540.2	B4DEX3

Frequencies

GnomAD3 genomes

AF:

0.531

AC:

80608

AN:

151936

Hom.:

21915

Cov.:

show subpopulations

Gnomad AFR

AF:

0.500

Gnomad AMI

AF:

0.707

Gnomad AMR

AF:

0.402

Gnomad ASJ

AF:

0.723

Gnomad EAS

AF:

0.340

Gnomad SAS

AF:

0.556

Gnomad FIN

AF:

0.489

Gnomad MID

AF:

0.415

Gnomad NFE

AF:

0.586

Gnomad OTH

AF:

0.521

GnomAD2 exomes

AF:

0.514

AC:

127533

AN:

248346

AF XY:

0.527

show subpopulations

Gnomad AFR exome

AF:

0.497

Gnomad AMR exome

AF:

0.266

Gnomad ASJ exome

AF:

0.729

Gnomad EAS exome

AF:

0.340

Gnomad FIN exome

AF:

0.494

Gnomad NFE exome

AF:

0.591

Gnomad OTH exome

AF:

0.529

GnomAD4 exome

AF:

0.569

AC:

830346

AN:

1458348

Hom.:

241583

Cov.:

AF XY:

0.570

AC XY:

413409

AN XY:

725388

show subpopulations

African (AFR)

AF:

0.503

AC:

16835

AN:

33436

American (AMR)

AF:

0.282

AC:

12572

AN:

44536

Ashkenazi Jewish (ASJ)

AF:

0.730

AC:

19053

AN:

26088

East Asian (EAS)

AF:

0.302

AC:

11961

AN:

39648

South Asian (SAS)

AF:

0.562

AC:

48133

AN:

85704

European-Finnish (FIN)

AF:

0.500

AC:

26668

AN:

53304

Middle Eastern (MID)

AF:

0.507

AC:

2902

AN:

5728

European-Non Finnish (NFE)

AF:

0.593

AC:

657809

AN:

1109646

Other (OTH)

AF:

0.571

AC:

34413

AN:

60258

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

18686

37371

56057

74742

93428

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17860

35720

53580

71440

89300

<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:

0.530

AC:

80635

AN:

152054

Hom.:

21928

Cov.:

AF XY:

0.522

AC XY:

38821

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.500

AC:

20726

AN:

41472

American (AMR)

AF:

0.401

AC:

6124

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.723

AC:

2508

AN:

3470

East Asian (EAS)

AF:

0.340

AC:

1748

AN:

5148

South Asian (SAS)

AF:

0.556

AC:

2685

AN:

4830

European-Finnish (FIN)

AF:

0.489

AC:

5166

AN:

10562

Middle Eastern (MID)

AF:

0.415

AC:

122

AN:

294

European-Non Finnish (NFE)

AF:

0.586

AC:

39819

AN:

67978

Other (OTH)

AF:

0.516

AC:

1092

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1940

3879

5819

7758

9698

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

704

1408

2112

2816

3520

<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:

0.584

Hom.:

8448

Bravo

AF:

0.522

Asia WGS

AF:

0.436

AC:

1522

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

-0.82

CADD

Benign

6.3

(source)

DANN

Benign

0.44

PhyloP100

0.23

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000033

dbscSNV1_RF

Benign

0.0

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