chr2-20006087-G-A

Variant names:

• chr2-20006087-G-A
• rs28598872
• NM_002381.5:c.447C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002381.5(MATN3):​c.447C>T​(p.Ala149Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 1,613,562 control chromosomes in the GnomAD database, including 163,762 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (17151 hom., cov: 32)
  • Exomes 𝑓: 0.44 (146611 hom.)
• Consequence: MATN3 NM_002381.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -5.19
• Publications: 18 publications found

Genes affected

MATN3 (HGNC:6909): (matrilin 3) This gene encodes a member of von Willebrand factor A domain containing protein family. This family of proteins is thought to be involved in the formation of filamentous networks in the extracellular matrices of various tissues. This protein contains two von Willebrand factor A domains; it is present in the cartilage extracellular matrix and has a role in the development and homeostasis of cartilage and bone. Mutations in this gene result in multiple epiphyseal dysplasia. [provided by RefSeq, Jul 2008]

MATN3 Gene-Disease associations (from GenCC):

• multiple epiphyseal dysplasia type 5

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, G2P, Labcorp Genetics (formerly Invitae)
• spondyloepimetaphyseal dysplasia, matrilin-3 type

  Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 2-20006087-G-A is Benign according to our data. Variant chr2-20006087-G-A is described in ClinVar as Benign. ClinVar VariationId is 195169.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.19 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002381.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MATN3	NM_002381.5	MANE Select	c.447C>T	p.Ala149Ala	synonymous	Exon 2 of 8	NP_002372.1	O15232-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MATN3	ENST00000407540.8	TSL:1 MANE Select	c.447C>T	p.Ala149Ala	synonymous	Exon 2 of 8	ENSP00000383894.3	O15232-1
	MATN3	ENST00000421259.2	TSL:1	c.447C>T	p.Ala149Ala	synonymous	Exon 2 of 7	ENSP00000398753.2	O15232-2
	MATN3	ENST00000856777.1		c.447C>T	p.Ala149Ala	synonymous	Exon 2 of 8	ENSP00000526836.1

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71491 AN: 151854 Hom.: 17127 Cov.: 32

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.477

GnomAD2 exomes AF: 0.475 AC: 118253 AN: 249030 AF XY: 0.477

Gnomad AFR exome AF: 0.519

Gnomad AMR exome AF: 0.493

Gnomad ASJ exome AF: 0.414

Gnomad EAS exome AF: 0.632

Gnomad FIN exome AF: 0.438

Gnomad NFE exome AF: 0.419

Gnomad OTH exome AF: 0.466

GnomAD4 exome AF: 0.443 AC: 647721 AN: 1461590 Hom.: 146611 Cov.: 57 AF XY: 0.447 AC XY: 324843 AN XY: 727076

African (AFR) AF: 0.530 AC: 17754 AN: 33480

American (AMR) AF: 0.487 AC: 21788 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.421 AC: 11016 AN: 26136

East Asian (EAS) AF: 0.695 AC: 27580 AN: 39694

South Asian (SAS) AF: 0.588 AC: 50756 AN: 86254

European-Finnish (FIN) AF: 0.432 AC: 23072 AN: 53400

Middle Eastern (MID) AF: 0.497 AC: 2865 AN: 5768

European-Non Finnish (NFE) AF: 0.419 AC: 465693 AN: 1111784

Other (OTH) AF: 0.451 AC: 27197 AN: 60364

GnomAD4 genome AF: 0.471 AC: 71565 AN: 151972 Hom.: 17151 Cov.: 32 AF XY: 0.476 AC XY: 35311 AN XY: 74254

African (AFR) AF: 0.521 AC: 21585 AN: 41444

American (AMR) AF: 0.496 AC: 7574 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1418 AN: 3468

East Asian (EAS) AF: 0.637 AC: 3276 AN: 5146

South Asian (SAS) AF: 0.587 AC: 2824 AN: 4812

European-Finnish (FIN) AF: 0.433 AC: 4565 AN: 10552

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.422 AC: 28699 AN: 67960

Other (OTH) AF: 0.483 AC: 1020 AN: 2110

Alfa AF: 0.437 Hom.: 9363

Bravo AF: 0.472

Asia WGS AF: 0.621 AC: 2158 AN: 3478

EpiCase AF: 0.423

EpiControl AF: 0.425

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	Multiple epiphyseal dysplasia type 5 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.35
DANN	Benign	0.78
PhyloP100		-5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	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: rs28598872; hg19: chr2-20205848; COSMIC: COSV68099878; COSMIC: COSV68099878;