NM_002380.5:c.593A>G

Variant names:

• chr8-97931403-A-G
• NM_002380.5:c.593A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002380.5(MATN2):​c.593A>G​(p.Gln198Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MATN2 NM_002380.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.45

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08442277).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MATN2	NM_002380.5	c.593A>G	p.Gln198Arg	missense_variant	Exon 3 of 19	ENST00000254898.7	NP_002371.3
MATN2	NM_030583.4	c.593A>G	p.Gln198Arg	missense_variant	Exon 3 of 19		NP_085072.2
MATN2	NM_001317748.2	c.593A>G	p.Gln198Arg	missense_variant	Exon 3 of 18		NP_001304677.1
MATN2	XM_005250920.3	c.593A>G	p.Gln198Arg	missense_variant	Exon 3 of 18		XP_005250977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MATN2	ENST00000254898.7	c.593A>G	p.Gln198Arg	missense_variant	Exon 3 of 19	1	NM_002380.5	ENSP00000254898.6
MATN2	ENST00000520016.5	c.593A>G	p.Gln198Arg	missense_variant	Exon 2 of 18	1		ENSP00000430487.1
MATN2	ENST00000521689.5	c.593A>G	p.Gln198Arg	missense_variant	Exon 3 of 19	1		ENSP00000429977.1
MATN2	ENST00000524308.5	c.593A>G	p.Gln198Arg	missense_variant	Exon 3 of 18	1		ENSP00000430221.1
MATN2	ENST00000518154.5	c.62A>G	p.Gln21Arg	missense_variant	Exon 1 of 16	1		ENSP00000429622.1
MATN2	ENST00000522025.6	c.-115+863A>G		intron_variant	Intron 2 of 17	5		ENSP00000429010.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.593A>G (p.Q198R) alteration is located in exon 3 (coding exon 2) of the MATN2 gene. This alteration results from a A to G substitution at nucleotide position 593, causing the glutamine (Q) at amino acid position 198 to be replaced by an arginine (R). 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	Benign	0.10
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	18
DANN	Benign	0.43
DEOGEN2	Benign	0.070	.;T;.;T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.051
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.64	T;T;T;.
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.084	T;T;T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	-1.3	N;N;N;N
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	2.5	N;N;N;N
REVEL	Uncertain	0.33
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0010	B;B;.;B
Vest4		0.056
MutPred		0.69		Gain of MoRF binding (P = 0.203);Gain of MoRF binding (P = 0.203);Gain of MoRF binding (P = 0.203);Gain of MoRF binding (P = 0.203);
MVP		0.75
MPC		0.21
ClinPred		0.63	D
GERP RS		6.0
Varity_R		0.069
gMVP		0.55

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: chr8-98943631;