rs28452699

Variant names:

• chr2-20003168-C-T
• rs28452699
• NM_002381.5:c.909G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-20003168-C-T
• chr2-20003168-C-A
• chr2-20003168-C-G

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.909G>A​(p.Thr303Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 1,613,434 control chromosomes in the GnomAD database, including 38,078 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3189 hom., cov: 32)
  • Exomes 𝑓: 0.22 (34889 hom.)
• Consequence: MATN3 NM_002381.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -3.74
• Publications: 12 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]

WDR35-DT (HGNC:55818): (WDR35 divergent transcript)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 2-20003168-C-T is Benign according to our data. Variant chr2-20003168-C-T is described in ClinVar as Benign. ClinVar VariationId is 258649.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.74 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.221 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.909G>A	p.Thr303Thr	synonymous	Exon 3 of 8	NP_002372.1	O15232-1
	WDR35-DT	NR_110235.1		n.364-852C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MATN3	ENST00000407540.8	TSL:1 MANE Select	c.909G>A	p.Thr303Thr	synonymous	Exon 3 of 8	ENSP00000383894.3	O15232-1
	MATN3	ENST00000421259.2	TSL:1	c.791-1088G>A		intron	N/A	ENSP00000398753.2	O15232-2
	MATN3	ENST00000856777.1		c.909G>A	p.Thr303Thr	synonymous	Exon 3 of 8	ENSP00000526836.1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30046 AN: 151980 Hom.: 3184 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.0326

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.197

GnomAD2 exomes AF: 0.204 AC: 50833 AN: 249116 AF XY: 0.203

Gnomad AFR exome AF: 0.155

Gnomad AMR exome AF: 0.240

Gnomad ASJ exome AF: 0.192

Gnomad EAS exome AF: 0.0284

Gnomad FIN exome AF: 0.253

Gnomad NFE exome AF: 0.225

Gnomad OTH exome AF: 0.211

GnomAD4 exome AF: 0.215 AC: 314342 AN: 1461334 Hom.: 34889 Cov.: 32 AF XY: 0.214 AC XY: 155473 AN XY: 726964

African (AFR) AF: 0.156 AC: 5237 AN: 33474

American (AMR) AF: 0.234 AC: 10483 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 5030 AN: 26130

East Asian (EAS) AF: 0.0504 AC: 2002 AN: 39698

South Asian (SAS) AF: 0.183 AC: 15750 AN: 86242

European-Finnish (FIN) AF: 0.251 AC: 13397 AN: 53370

Middle Eastern (MID) AF: 0.174 AC: 1000 AN: 5760

European-Non Finnish (NFE) AF: 0.224 AC: 249171 AN: 1111600

Other (OTH) AF: 0.203 AC: 12272 AN: 60350

GnomAD4 genome AF: 0.198 AC: 30083 AN: 152100 Hom.: 3189 Cov.: 32 AF XY: 0.198 AC XY: 14744 AN XY: 74370

African (AFR) AF: 0.159 AC: 6611 AN: 41494

American (AMR) AF: 0.216 AC: 3298 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 641 AN: 3466

East Asian (EAS) AF: 0.0327 AC: 169 AN: 5172

South Asian (SAS) AF: 0.180 AC: 870 AN: 4828

European-Finnish (FIN) AF: 0.254 AC: 2684 AN: 10572

Middle Eastern (MID) AF: 0.0822 AC: 24 AN: 292

European-Non Finnish (NFE) AF: 0.224 AC: 15246 AN: 67960

Other (OTH) AF: 0.195 AC: 412 AN: 2112

Alfa AF: 0.210 Hom.: 5183

Bravo AF: 0.193

Asia WGS AF: 0.122 AC: 424 AN: 3478

EpiCase AF: 0.214

EpiControl AF: 0.213

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	1.6
DANN	Benign	0.81
PhyloP100		-3.7
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: rs28452699; hg19: chr2-20202929; COSMIC: COSV68099679;