4-87612894-T-C

Variant names:

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.708T>C(p.Asp236Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00783 in 1,614,036 control chromosomes in the GnomAD database, including 898 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.042 ( 452 hom., cov: 32)

Exomes 𝑓: 0.0042 ( 446 hom. )

Consequence

DSPP
NM_014208.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0620

Publications

2 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=-0.55).

BP6

Variant 4-87612894-T-C is Benign according to our data. Variant chr4-87612894-T-C is described in ClinVar as Benign. ClinVar VariationId is 260358.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.062 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSPP	NM_014208.3 link	c.708T>C	p.Asp236Asp	synonymous_variant	Exon 4 of 5	ENST00000651931.1	NP_055023.2
DMP1-AS1	NR_198971.1 link	n.367-44361A>G		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSPP	ENST00000651931.1 link	c.708T>C	p.Asp236Asp	synonymous_variant	Exon 4 of 5		NM_014208.3	ENSP00000498766.1

Frequencies

GnomAD3 genomes

AF:

0.0423

AC:

6428

AN:

152042

Hom.:

452

Cov.:

show subpopulations

Gnomad AFR

AF:

0.147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0174

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.0301

GnomAD2 exomes

AF:

0.0108

AC:

2693

AN:

249470

AF XY:

0.00818

show subpopulations

Gnomad AFR exome

AF:

0.156

Gnomad AMR exome

AF:

0.00672

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000971

Gnomad OTH exome

AF:

0.00363

GnomAD4 exome

AF:

0.00423

AC:

6184

AN:

1461876

Hom.:

446

Cov.:

AF XY:

0.00361

AC XY:

2627

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.153

AC:

5114

AN:

33480

American (AMR)

AF:

0.00823

AC:

368

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.000383

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00329

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000998

AC:

111

AN:

1112002

Other (OTH)

AF:

0.00892

AC:

539

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

389

777

1166

1554

1943

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

154

308

462

616

770

<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:

0.0424

AC:

6452

AN:

152160

Hom.:

452

Cov.:

AF XY:

0.0407

AC XY:

3028

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.147

AC:

6091

AN:

41486

American (AMR)

AF:

0.0173

AC:

264

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000831

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000426

AC:

AN:

68008

Other (OTH)

AF:

0.0298

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

282

563

845

1126

1408

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

204

272

340

<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:

0.0216

Hom.:

132

Bravo

AF:

0.0489

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

May 24, 2018

Athena Diagnostics

Significance:Benign