2-19998305-G-A

Position:

• chr2-19998305-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002381.5(MATN3):​c.1169-1046C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 151,798 control chromosomes in the GnomAD database, including 25,532 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 0.57 (25532 hom., cov: 31)
• Consequence: MATN3 NM_002381.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MATN3	NM_002381.5	c.1169-1046C>T		intron_variant		ENST00000407540.8	NP_002372.1
WDR35-DT	NR_110235.1	n.292-901G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MATN3	ENST00000407540.8	c.1169-1046C>T		intron_variant		1	NM_002381.5	ENSP00000383894	P1
MATN3	ENST00000421259.2	c.1043-1046C>T		intron_variant		1		ENSP00000398753
WDR35-DT	ENST00000416575.2	n.285-901G>A		intron_variant, non_coding_transcript_variant		2
WDR35-DT	ENST00000658200.1	n.287-901G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86508 AN: 151680 Hom.: 25488 Cov.: 31

Gnomad AFR AF: 0.719

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.545

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.571 AC: 86612 AN: 151798 Hom.: 25532 Cov.: 31 AF XY: 0.572 AC XY: 42408 AN XY: 74166

Gnomad4 AFR AF: 0.719

Gnomad4 AMR AF: 0.547

Gnomad4 ASJ AF: 0.455

Gnomad4 EAS AF: 0.665

Gnomad4 SAS AF: 0.621

Gnomad4 FIN AF: 0.482

Gnomad4 NFE AF: 0.495

Gnomad4 OTH AF: 0.551

Alfa AF: 0.514 Hom.: 5280

Bravo AF: 0.577

Asia WGS AF: 0.658 AC: 2288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.18
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs10178256; hg19: chr2-20198066;