rs2615497

Positions:

Variant summary

Our verdict is Benign. Variant got -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

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 links:

DMP1 (HGNC:):

DMP1 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=-0.7).

BP6

Variant 4-87663008-G-A is Benign according to our data. Variant chr4-87663008-G-A is described in ClinVar as [Benign]. Clinvar id is 349983.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-87663008-G-A is described in Lovd as [Benign]. Variant chr4-87663008-G-A is described in Lovd as [Likely_benign].

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/exons	MANE	Protein	UniProt
DMP1	NM_004407.4 linkuse as main transcript	c.1230G>A	p.Glu410Glu	synonymous_variant	6/6	ENST00000339673.11	NP_004398.1	Q13316-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMP1	ENST00000339673.11 linkuse as main transcript	c.1230G>A	p.Glu410Glu	synonymous_variant	6/6	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

GnomAD3 exomes

AF:

0.250

AC:

62591

AN:

250854

Hom.:

8423

AF XY:

0.255

AC XY:

34626

AN XY:

135646

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 SAS exome

AF:

0.351

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

Gnomad4 AFR exome

AF:

0.412

Gnomad4 AMR exome

AF:

0.156

Gnomad4 ASJ exome

AF:

0.187

Gnomad4 EAS exome

AF:

0.248

Gnomad4 SAS exome

AF:

0.349

Gnomad4 FIN exome

AF:

0.275

Gnomad4 NFE exome

AF:

0.229

Gnomad4 OTH exome

AF:

0.253

GnomAD4 genome

AF:

0.280

AC:

42557

AN:

151992

Hom.:

6500

Cov.:

AF XY:

0.282

AC XY:

20981

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.399

Gnomad4 AMR

AF:

0.215

Gnomad4 ASJ

AF:

0.183

Gnomad4 EAS

AF:

0.257

Gnomad4 SAS

AF:

0.340

Gnomad4 FIN

AF:

0.268

Gnomad4 NFE

AF:

0.228

Gnomad4 OTH

AF:

0.268

Alfa

AF:

0.227

Hom.:

2242

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Hypophosphatemic rickets, autosomal recessive, 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

1.1

DANN

Benign

0.52

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