11-102577525-A-G

Variant names:

• chr11-102577525-A-G
• rs2292730
• NM_004771.4:c.1352-99T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004771.4(MMP20):​c.1352-99T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 843,940 control chromosomes in the GnomAD database, including 144,235 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.63 (30524 hom., cov: 33)
  • Exomes 𝑓: 0.57 (113711 hom.)
• Consequence: MMP20 NM_004771.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.50
• Publications: 17 publications found

Genes affected

MMP20 (HGNC:7167): (matrix metallopeptidase 20) Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. The protein encoded by this gene degrades amelogenin, the major protein component of dental enamel matrix, and thus thought to play a role in tooth enamel formation. A mutation in this gene, which alters the normal splice pattern and results in premature termination of the encoded protein, has been associated with amelogenesis imperfecta. This gene is part of a cluster of MMP genes located on chromosome 11q22.3. [provided by RefSeq, Aug 2011]

MMP20 Gene-Disease associations (from GenCC):

• amelogenesis imperfecta hypomaturation type 2A2

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• amelogenesis imperfecta type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 11-102577525-A-G is Benign according to our data. Variant chr11-102577525-A-G is described in ClinVar as [Benign]. Clinvar id is 1262923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP20	NM_004771.4	c.1352-99T>C		intron_variant	Intron 9 of 9	ENST00000260228.3	NP_004762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP20	ENST00000260228.3	c.1352-99T>C		intron_variant	Intron 9 of 9	1	NM_004771.4	ENSP00000260228.2
MMP20	ENST00000542305.1	n.250-99T>C		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95237 AN: 152002 Hom.: 30481 Cov.: 33

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.599

GnomAD4 exome AF: 0.568 AC: 392617 AN: 691820 Hom.: 113711 AF XY: 0.561 AC XY: 205754 AN XY: 366540

African (AFR) AF: 0.756 AC: 13672 AN: 18074

American (AMR) AF: 0.586 AC: 20443 AN: 34864

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 10955 AN: 20476

East Asian (EAS) AF: 0.786 AC: 25197 AN: 32072

South Asian (SAS) AF: 0.482 AC: 31456 AN: 65202

European-Finnish (FIN) AF: 0.625 AC: 28756 AN: 46004

Middle Eastern (MID) AF: 0.564 AC: 1595 AN: 2830

European-Non Finnish (NFE) AF: 0.549 AC: 240607 AN: 438070

Other (OTH) AF: 0.582 AC: 19936 AN: 34228

GnomAD4 genome AF: 0.627 AC: 95331 AN: 152120 Hom.: 30524 Cov.: 33 AF XY: 0.629 AC XY: 46751 AN XY: 74358

African (AFR) AF: 0.756 AC: 31404 AN: 41514

American (AMR) AF: 0.601 AC: 9194 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1852 AN: 3468

East Asian (EAS) AF: 0.756 AC: 3912 AN: 5172

South Asian (SAS) AF: 0.493 AC: 2376 AN: 4820

European-Finnish (FIN) AF: 0.640 AC: 6764 AN: 10570

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.559 AC: 38017 AN: 67964

Other (OTH) AF: 0.600 AC: 1267 AN: 2112

Alfa AF: 0.573 Hom.: 79320

Bravo AF: 0.632

Asia WGS AF: 0.633 AC: 2200 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

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	-0.93
CADD	Benign	0.64
DANN	Benign	0.48
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2292730; hg19: chr11-102448256; COSMIC: COSV52774928;