chr2-19993170-G-C

Position:

• chr2-19993170-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002381.5(MATN3):​c.1406-4C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MATN3 NM_002381.5 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0001137
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.331

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MATN3	NM_002381.5	c.1406-4C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000407540.8
WDR35-DT	NR_110235.1	n.291+2676G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MATN3	ENST00000407540.8	c.1406-4C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_002381.5	P1
MATN3	ENST00000421259.2	c.1280-4C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1
WDR35-DT	ENST00000416575.2	n.284+2676G>C		intron_variant, non_coding_transcript_variant		2
WDR35-DT	ENST00000658200.1	n.286+2676G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.1
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00011
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: rs35973216; hg19: chr2-20192931;