rs2736982

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -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

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 links:

ENSG00000249001 (HGNC:58144):

ENSG00000249001 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 260359.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-87613083-A-G is described in Lovd as [Benign].

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	Q9NZW4

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		Q9NZW4
ENSG00000249001	ENST00000506480.5 link	n.323-44550T>C		intron_variant	Intron 3 of 3	3

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

GnomAD3 exomes

AF:

0.626

AC:

156098

AN:

249262

Hom.:

49297

AF XY:

0.621

AC XY:

84038

AN XY:

135246

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 SAS exome

AF:

0.578

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

Gnomad4 AFR exome

AF:

0.741

Gnomad4 AMR exome

AF:

0.603

Gnomad4 ASJ exome

AF:

0.570

Gnomad4 EAS exome

AF:

0.638

Gnomad4 SAS exome

AF:

0.578

Gnomad4 FIN exome

AF:

0.681

Gnomad4 NFE exome

AF:

0.607

Gnomad4 OTH exome

AF:

0.619

GnomAD4 genome

AF:

0.647

AC:

98399

AN:

151992

Hom.:

32065

Cov.:

AF XY:

0.646

AC XY:

48024

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.730

Gnomad4 AMR

AF:

0.583

Gnomad4 ASJ

AF:

0.558

Gnomad4 EAS

AF:

0.688

Gnomad4 SAS

AF:

0.586

Gnomad4 FIN

AF:

0.680

Gnomad4 NFE

AF:

0.614

Gnomad4 OTH

AF:

0.645

Alfa

AF:

0.615

Hom.:

68540

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

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

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

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

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

DANN

Benign

0.53

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over