rs2736982

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014208.3(DSPP):c.897A>G(p.Ser299Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 1,613,822 control chromosomes in the GnomAD database, including 307,067 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 32065 hom., cov: 31)

Exomes 𝑓: 0.61 ( 275002 hom. )

Consequence

DSPP
NM_014208.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0520

Publications

27 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 -21 ACMG points.

BP4

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

BP6

Variant 4-87613083-A-G is Benign according to our data. Variant chr4-87613083-A-G is described in ClinVar as Benign. ClinVar VariationId is 260359.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.052 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSPP	NM_014208.3 link	c.897A>G	p.Ser299Ser	synonymous_variant	Exon 4 of 5	ENST00000651931.1	NP_055023.2
DMP1-AS1	NR_198971.1 link	n.367-44550T>C		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSPP	ENST00000651931.1 link	c.897A>G	p.Ser299Ser	synonymous_variant	Exon 4 of 5		NM_014208.3	ENSP00000498766.1

Frequencies

GnomAD3 genomes

AF:

0.647

AC:

98294

AN:

151874

Hom.:

32012

Cov.:

show subpopulations

Gnomad AFR

AF:

0.729

Gnomad AMI

AF:

0.526

Gnomad AMR

AF:

0.583

Gnomad ASJ

AF:

0.558

Gnomad EAS

AF:

0.687

Gnomad SAS

AF:

0.586

Gnomad FIN

AF:

0.680

Gnomad MID

AF:

0.728

Gnomad NFE

AF:

0.614

Gnomad OTH

AF:

0.640

GnomAD2 exomes

AF:

0.626

AC:

156098

AN:

249262

AF XY:

0.621

show subpopulations

Gnomad AFR exome

AF:

0.733

Gnomad AMR exome

AF:

0.607

Gnomad ASJ exome

AF:

0.568

Gnomad EAS exome

AF:

0.691

Gnomad FIN exome

AF:

0.687

Gnomad NFE exome

AF:

0.614

Gnomad OTH exome

AF:

0.625

GnomAD4 exome

AF:

0.612

AC:

894895

AN:

1461830

Hom.:

275002

Cov.:

AF XY:

0.611

AC XY:

444299

AN XY:

727210

show subpopulations

African (AFR)

AF:

0.741

AC:

24799

AN:

33480

American (AMR)

AF:

0.603

AC:

26944

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.570

AC:

14905

AN:

26132

East Asian (EAS)

AF:

0.638

AC:

25342

AN:

39698

South Asian (SAS)

AF:

0.578

AC:

49875

AN:

86256

European-Finnish (FIN)

AF:

0.681

AC:

36393

AN:

53416

Middle Eastern (MID)

AF:

0.675

AC:

3891

AN:

5768

European-Non Finnish (NFE)

AF:

0.607

AC:

675356

AN:

1111980

Other (OTH)

AF:

0.619

AC:

37390

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

25689

51377

77066

102754

128443

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18288

36576

54864

73152

91440

<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:

0.647

AC:

98399

AN:

151992

Hom.:

32065

Cov.:

AF XY:

0.646

AC XY:

48024

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.730

AC:

30220

AN:

41402

American (AMR)

AF:

0.583

AC:

8911

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.558

AC:

1936

AN:

3472

East Asian (EAS)

AF:

0.688

AC:

3548

AN:

5160

South Asian (SAS)

AF:

0.586

AC:

2819

AN:

4812

European-Finnish (FIN)

AF:

0.680

AC:

7188

AN:

10572

Middle Eastern (MID)

AF:

0.728

AC:

214

AN:

294

European-Non Finnish (NFE)

AF:

0.614

AC:

41721

AN:

67972

Other (OTH)

AF:

0.645

AC:

1363

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1792

3584

5376

7168

8960

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

798

1596

2394

3192

3990

<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:

0.622

Hom.:

103207

Bravo

AF:

0.647

Asia WGS

AF:

0.659

AC:

2294

AN:

3478

EpiCase

AF:

0.605

EpiControl

AF:

0.604

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

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

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

-0.87

CADD

Benign

0.76

(source)

DANN

Benign

0.53

PhyloP100

0.052

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

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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