rs2615497

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_004407.4(DMP1):c.1230G>A(p.Glu410Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,613,756 control chromosomes in the GnomAD database, including 50,444 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6500 hom., cov: 32)

Exomes 𝑓: 0.24 ( 43944 hom. )

Consequence

DMP1
NM_004407.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.80

Publications

18 publications found

Variant links:

Genes affected

DMP1 (HGNC:2932): (dentin matrix acidic phosphoprotein 1) Dentin matrix acidic phosphoprotein is an extracellular matrix protein and a member of the small integrin binding ligand N-linked glycoprotein family. This protein, which is critical for proper mineralization of bone and dentin, is present in diverse cells of bone and tooth tissues. The protein contains a large number of acidic domains, multiple phosphorylation sites, a functional arg-gly-asp cell attachment sequence, and a DNA binding domain. In undifferentiated osteoblasts it is primarily a nuclear protein that regulates the expression of osteoblast-specific genes. During osteoblast maturation the protein becomes phosphorylated and is exported to the extracellular matrix, where it orchestrates mineralized matrix formation. Mutations in the gene are known to cause autosomal recessive hypophosphatemia, a disease that manifests as rickets and osteomalacia. The gene structure is conserved in mammals. Two transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

DMP1 Gene-Disease associations (from GenCC):

hypophosphatemic rickets, autosomal recessive, 1
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
autosomal recessive hypophosphatemic rickets
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

DMP1 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=-0.7).

BP6

Variant 4-87663008-G-A is Benign according to our data. Variant chr4-87663008-G-A is described in ClinVar as Benign. ClinVar VariationId is 349983.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.8 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMP1	NM_004407.4 link	c.1230G>A	p.Glu410Glu	synonymous_variant	Exon 6 of 6	ENST00000339673.11	NP_004398.1	Q13316-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMP1	ENST00000339673.11 link	c.1230G>A	p.Glu410Glu	synonymous_variant	Exon 6 of 6	1	NM_004407.4	ENSP00000340935.6		Q13316-1

Frequencies

GnomAD3 genomes

AF:

0.280

AC:

42495

AN:

151874

Hom.:

6480

Cov.:

show subpopulations

Gnomad AFR

AF:

0.399

Gnomad AMI

AF:

0.179

Gnomad AMR

AF:

0.215

Gnomad ASJ

AF:

0.183

Gnomad EAS

AF:

0.257

Gnomad SAS

AF:

0.338

Gnomad FIN

AF:

0.268

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.228

Gnomad OTH

AF:

0.266

GnomAD2 exomes

AF:

0.250

AC:

62591

AN:

250854

AF XY:

0.255

show subpopulations

Gnomad AFR exome

AF:

0.402

Gnomad AMR exome

AF:

0.149

Gnomad ASJ exome

AF:

0.185

Gnomad EAS exome

AF:

0.251

Gnomad FIN exome

AF:

0.272

Gnomad NFE exome

AF:

0.233

Gnomad OTH exome

AF:

0.239

GnomAD4 exome

AF:

0.241

AC:

352055

AN:

1461764

Hom.:

43944

Cov.:

AF XY:

0.245

AC XY:

177868

AN XY:

727186

show subpopulations

African (AFR)

AF:

0.412

AC:

13783

AN:

33480

American (AMR)

AF:

0.156

AC:

6971

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.187

AC:

4877

AN:

26136

East Asian (EAS)

AF:

0.248

AC:

9859

AN:

39700

South Asian (SAS)

AF:

0.349

AC:

30097

AN:

86258

European-Finnish (FIN)

AF:

0.275

AC:

14664

AN:

53404

Middle Eastern (MID)

AF:

0.336

AC:

1939

AN:

5768

European-Non Finnish (NFE)

AF:

0.229

AC:

254597

AN:

1111904

Other (OTH)

AF:

0.253

AC:

15268

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

17518

35035

52553

70070

87588

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8882

17764

26646

35528

44410

<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:

0.280

AC:

42557

AN:

151992

Hom.:

6500

Cov.:

AF XY:

0.282

AC XY:

20981

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.399

AC:

16531

AN:

41448

American (AMR)

AF:

0.215

AC:

3285

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.183

AC:

635

AN:

3468

East Asian (EAS)

AF:

0.257

AC:

1325

AN:

5156

South Asian (SAS)

AF:

0.340

AC:

1638

AN:

4822

European-Finnish (FIN)

AF:

0.268

AC:

2833

AN:

10552

Middle Eastern (MID)

AF:

0.347

AC:

102

AN:

294

European-Non Finnish (NFE)

AF:

0.228

AC:

15478

AN:

67942

Other (OTH)

AF:

0.268

AC:

567

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1548

3096

4644

6192

7740

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

438

876

1314

1752

2190

<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:

0.229

Hom.:

2308

Bravo

AF:

0.278

Asia WGS

AF:

0.328

AC:

1139

AN:

3478

EpiCase

AF:

0.235

EpiControl

AF:

0.235

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

not specified

Benign:2

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

- -

Hypophosphatemic rickets, autosomal recessive, 1

Benign:2

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

1.1

(source)

DANN

Benign

0.52

PhyloP100

1.8

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