rs28401180

Variant names:

• chr2-20005919-C-T
• rs28401180
• NM_002381.5:c.615G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-20005919-C-T
• chr2-20005919-C-A
• chr2-20005919-C-G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_002381.5(MATN3):​c.615G>A​(p.Glu205Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 1,612,252 control chromosomes in the GnomAD database, including 163,336 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (17086 hom., cov: 32)
  • Exomes 𝑓: 0.44 (146250 hom.)
• Consequence: MATN3 NM_002381.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.310
• Publications: 16 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 2-20005919-C-T is Benign according to our data. Variant chr2-20005919-C-T is described in ClinVar as Benign. ClinVar VariationId is 195170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.31 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.619 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.615G>A	p.Glu205Glu	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.615G>A	p.Glu205Glu	synonymous	Exon 2 of 8	ENSP00000383894.3	O15232-1
	MATN3	ENST00000421259.2	TSL:1	c.615G>A	p.Glu205Glu	synonymous	Exon 2 of 7	ENSP00000398753.2	O15232-2
	MATN3	ENST00000856777.1		c.615G>A	p.Glu205Glu	synonymous	Exon 2 of 8	ENSP00000526836.1

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71353 AN: 151926 Hom.: 17062 Cov.: 32

Gnomad AFR AF: 0.519

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: 0.430

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.476

GnomAD2 exomes AF: 0.473 AC: 116386 AN: 245802 AF XY: 0.475

Gnomad AFR exome AF: 0.515

Gnomad AMR exome AF: 0.493

Gnomad ASJ exome AF: 0.414

Gnomad EAS exome AF: 0.631

Gnomad FIN exome AF: 0.435

Gnomad NFE exome AF: 0.418

Gnomad OTH exome AF: 0.467

GnomAD4 exome AF: 0.443 AC: 646821 AN: 1460206 Hom.: 146250 Cov.: 63 AF XY: 0.447 AC XY: 324334 AN XY: 726294

African (AFR) AF: 0.528 AC: 17670 AN: 33458

American (AMR) AF: 0.487 AC: 21624 AN: 44400

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 11008 AN: 26108

East Asian (EAS) AF: 0.695 AC: 27569 AN: 39644

South Asian (SAS) AF: 0.588 AC: 50673 AN: 86120

European-Finnish (FIN) AF: 0.430 AC: 22933 AN: 53320

Middle Eastern (MID) AF: 0.496 AC: 2860 AN: 5764

European-Non Finnish (NFE) AF: 0.419 AC: 465317 AN: 1111058

Other (OTH) AF: 0.450 AC: 27167 AN: 60334

GnomAD4 genome AF: 0.470 AC: 71427 AN: 152046 Hom.: 17086 Cov.: 32 AF XY: 0.474 AC XY: 35269 AN XY: 74336

African (AFR) AF: 0.519 AC: 21516 AN: 41470

American (AMR) AF: 0.496 AC: 7574 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1418 AN: 3470

East Asian (EAS) AF: 0.637 AC: 3283 AN: 5156

South Asian (SAS) AF: 0.587 AC: 2830 AN: 4822

European-Finnish (FIN) AF: 0.430 AC: 4545 AN: 10574

Middle Eastern (MID) AF: 0.408 AC: 119 AN: 292

European-Non Finnish (NFE) AF: 0.421 AC: 28642 AN: 67960

Other (OTH) AF: 0.481 AC: 1015 AN: 2108

Alfa AF: 0.432 Hom.: 21818

Bravo AF: 0.471

Asia WGS AF: 0.621 AC: 2158 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	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	-0.39
CADD	Benign	8.0
DANN	Benign	0.71
PhyloP100		-0.31
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: rs28401180; hg19: chr2-20205680; COSMIC: COSV68100410; COSMIC: COSV68100410;