rs2615489

Variant names:

Variant summary

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

The NM_014208.3(DSPP):c.*17G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.863 in 1,551,650 control chromosomes in the GnomAD database, including 579,143 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.87 ( 58082 hom., cov: 33)

Exomes 𝑓: 0.86 ( 521061 hom. )

Consequence

DSPP
NM_014208.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.201

Publications

13 publications found

Variant links:

Genes affected

DSPP (HGNC:3054): (dentin sialophosphoprotein) This gene encodes a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family of proteins. The encoded preproprotein is secreted by odontoblasts and proteolytically processed to generate two principal proteins of the dentin extracellular matrix of the tooth, dentin sialoprotein and dentin phosphoprotein. These two protein products may play distinct but related roles in dentin mineralization. Mutations in this gene are associated with dentinogenesis imperfecta and dentin dysplasia. This gene is present in a gene cluster on chromosome 4. Allelic differences due to repeat polymorphisms have been found for this gene. [provided by RefSeq, Jan 2016]

DSPP Gene-Disease associations (from GenCC):

deafness, autosomal dominant 39, with dentinogenesis imperfecta 1
Inheritance: AD, Unknown Classification: DEFINITIVE, MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
dentinogenesis imperfecta
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
dentinogenesis imperfecta type 2
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
dentinogenesis imperfecta type 3
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
dentin dysplasia type I
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
dentin dysplasia type II
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DSPP links:

ENSG00000249001 (HGNC:58144):

ENSG00000249001 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=-0.91).

BP6

Variant 4-87616585-G-A is Benign according to our data. Variant chr4-87616585-G-A is described in ClinVar as Benign. ClinVar VariationId is 260353.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSPP	NM_014208.3 link	c.*17G>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000651931.1	NP_055023.2	Q9NZW4
DMP1-AS1	NR_198971.1 link	n.367-48052C>T		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSPP	ENST00000651931.1 link	c.*17G>A		3_prime_UTR_variant	Exon 5 of 5		NM_014208.3	ENSP00000498766.1		Q9NZW4

Frequencies

GnomAD3 genomes

AF:

0.872

AC:

132705

AN:

152158

Hom.:

58018

Cov.:

show subpopulations

Gnomad AFR

AF:

0.897

Gnomad AMI

AF:

0.734

Gnomad AMR

AF:

0.899

Gnomad ASJ

AF:

0.738

Gnomad EAS

AF:

0.876

Gnomad SAS

AF:

0.719

Gnomad FIN

AF:

0.884

Gnomad MID

AF:

0.820

Gnomad NFE

AF:

0.868

Gnomad OTH

AF:

0.871

GnomAD2 exomes

AF:

0.850

AC:

131246

AN:

154370

AF XY:

0.838

show subpopulations

Gnomad AFR exome

AF:

0.896

Gnomad AMR exome

AF:

0.929

Gnomad ASJ exome

AF:

0.743

Gnomad EAS exome

AF:

0.888

Gnomad FIN exome

AF:

0.886

Gnomad NFE exome

AF:

0.864

Gnomad OTH exome

AF:

0.847

GnomAD4 exome

AF:

0.862

AC:

1205653

AN:

1399374

Hom.:

521061

Cov.:

AF XY:

0.856

AC XY:

590847

AN XY:

690188

show subpopulations

African (AFR)

AF:

0.896

AC:

28319

AN:

31598

American (AMR)

AF:

0.923

AC:

32958

AN:

35704

Ashkenazi Jewish (ASJ)

AF:

0.743

AC:

18704

AN:

25182

East Asian (EAS)

AF:

0.846

AC:

30220

AN:

35738

South Asian (SAS)

AF:

0.717

AC:

56774

AN:

79234

European-Finnish (FIN)

AF:

0.881

AC:

43406

AN:

49264

Middle Eastern (MID)

AF:

0.794

AC:

4526

AN:

5698

European-Non Finnish (NFE)

AF:

0.872

AC:

941227

AN:

1078958

Other (OTH)

AF:

0.854

AC:

49519

AN:

57998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

11508

23016

34523

46031

57539

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20926

41852

62778

83704

104630

<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:

0.872

AC:

132827

AN:

152276

Hom.:

58082

Cov.:

AF XY:

0.870

AC XY:

64753

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.898

AC:

37293

AN:

41548

American (AMR)

AF:

0.899

AC:

13763

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.738

AC:

2563

AN:

3472

East Asian (EAS)

AF:

0.877

AC:

4542

AN:

5178

South Asian (SAS)

AF:

0.718

AC:

3464

AN:

4826

European-Finnish (FIN)

AF:

0.884

AC:

9374

AN:

10604

Middle Eastern (MID)

AF:

0.813

AC:

239

AN:

294

European-Non Finnish (NFE)

AF:

0.868

AC:

59072

AN:

68024

Other (OTH)

AF:

0.874

AC:

1849

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

887

1774

2661

3548

4435

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

896

1792

2688

3584

4480

<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:

0.865

Hom.:

152455

Bravo

AF:

0.877

Asia WGS

AF:

0.819

AC:

2847

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jun 26, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 29, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dentinogenesis imperfecta type 3

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Denticles

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dentinogenesis imperfecta type 2

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Deafness, autosomal dominant 39, with dentinogenesis imperfecta 1

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.71

(source)

DANN

Benign

0.62

PhyloP100

-0.20

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over