chr8-97930999-C-G

Position:

• chr8-97930999-C-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_002380.5(MATN2):​c.189C>G​(p.Asp63Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MATN2 NM_002380.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.76

Genes affected

MATN2 (HGNC:6908): (matrilin 2) This gene encodes a member of the 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 five von Willebrand factor A domains. The specific function of this gene has not yet been determined. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MATN2 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.982

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MATN2	NM_002380.5	c.189C>G	p.Asp63Glu	missense_variant	3/19	ENST00000254898.7	NP_002371.3
MATN2	NM_030583.4	c.189C>G	p.Asp63Glu	missense_variant	3/19		NP_085072.2
MATN2	NM_001317748.2	c.189C>G	p.Asp63Glu	missense_variant	3/18		NP_001304677.1
MATN2	XM_005250920.3	c.189C>G	p.Asp63Glu	missense_variant	3/18		XP_005250977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MATN2	ENST00000254898.7	c.189C>G	p.Asp63Glu	missense_variant	3/19	1	NM_002380.5	ENSP00000254898.6
MATN2	ENST00000520016.5	c.189C>G	p.Asp63Glu	missense_variant	2/18	1		ENSP00000430487.1
MATN2	ENST00000521689.5	c.189C>G	p.Asp63Glu	missense_variant	3/19	1		ENSP00000429977.1
MATN2	ENST00000524308.5	c.189C>G	p.Asp63Glu	missense_variant	3/18	1		ENSP00000430221.1
MATN2	ENST00000522025.6	c.-115+459C>G		intron_variant		5		ENSP00000429010.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 10, 2024

The c.189C>G (p.D63E) alteration is located in exon 3 (coding exon 2) of the MATN2 gene. This alteration results from a C to G substitution at nucleotide position 189, causing the aspartic acid (D) at amino acid position 63 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.51	D
BayesDel_noAF	Pathogenic	0.50
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.57	.;D;.;D
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.99	D;D;D;.
M_CAP	Pathogenic	0.58	D
MetaRNN	Pathogenic	0.98	D;D;D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	2.9	M;M;M;M
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-3.5	D;D;D;D
REVEL	Pathogenic	0.95
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	D;D;.;D
Vest4		0.99
MutPred		0.86		Gain of disorder (P = 0.2215);Gain of disorder (P = 0.2215);Gain of disorder (P = 0.2215);Gain of disorder (P = 0.2215);
MVP		0.97
MPC		0.73
ClinPred		0.99	D
GERP RS		3.9
Varity_R		0.88
gMVP		0.92

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-98943227;