2-20004293-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_002381.5(MATN3):c.791-1007G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 152,156 control chromosomes in the GnomAD database, including 5,060 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.24 (5060 hom., cov: 32)
  • Exomes 𝑓: 0.14 (0 hom.)
• Consequence: MATN3 NM_002381.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MATN3	NM_002381.5	c.791-1007G>A		intron_variant		ENST00000407540.8
WDR35-DT	NR_110235.1	n.637C>T		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MATN3	ENST00000407540.8	c.791-1007G>A		intron_variant		1	NM_002381.5	P1
MATN3	ENST00000421259.2	c.790+1451G>A		intron_variant		1
WDR35-DT	ENST00000416575.2	n.630C>T		non_coding_transcript_exon_variant	3/3	2
WDR35-DT	ENST00000658200.1	n.3350C>T		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36809 AN: 152016 Hom.: 5055 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.252

GnomAD4 exome AF: 0.136 AC: 3 AN: 22 Hom.: 0 AF XY: 0.167 AC XY: 3 AN XY: 18

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.188

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.242 AC: 36830 AN: 152134 Hom.: 5060 Cov.: 32 AF XY: 0.247 AC XY: 18389 AN XY: 74384

Gnomad4 AFR AF: 0.256

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.616

Gnomad4 SAS AF: 0.391

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.260

Alfa AF: 0.214 Hom.: 1681

Bravo AF: 0.245

Asia WGS AF: 0.491 AC: 1706 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
Cadd	Benign	17
Dann	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

Other links and lift over

dbSNP: rs11096633; hg19: chr2-20204054;