8-97961462-T-G

Position:

• chr8-97961462-T-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.890T>G​(p.Val297Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: MATN2 NM_002380.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.78

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 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=0.25127414).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MATN2	NM_002380.5	c.890T>G	p.Val297Gly	missense_variant	5/19	ENST00000254898.7	NP_002371.3
MATN2	NM_030583.4	c.890T>G	p.Val297Gly	missense_variant	5/19		NP_085072.2
MATN2	NM_001317748.2	c.890T>G	p.Val297Gly	missense_variant	5/18		NP_001304677.1
MATN2	XM_005250920.3	c.890T>G	p.Val297Gly	missense_variant	5/18		XP_005250977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MATN2	ENST00000254898.7	c.890T>G	p.Val297Gly	missense_variant	5/19	1	NM_002380.5	ENSP00000254898.6
MATN2	ENST00000520016.5	c.890T>G	p.Val297Gly	missense_variant	4/18	1		ENSP00000430487.1
MATN2	ENST00000521689.5	c.890T>G	p.Val297Gly	missense_variant	5/19	1		ENSP00000429977.1
MATN2	ENST00000524308.5	c.890T>G	p.Val297Gly	missense_variant	5/18	1		ENSP00000430221.1
MATN2	ENST00000522025.6	c.38T>G	p.Val13Gly	missense_variant	4/18	5		ENSP00000429010.1
MATN2	ENST00000518154.5	c.305-17424T>G		intron_variant		1		ENSP00000429622.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461554 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727054

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000630

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Nov 09, 2024

The c.890T>G (p.V297G) alteration is located in exon 5 (coding exon 4) of the MATN2 gene. This alteration results from a T to G substitution at nucleotide position 890, causing the valine (V) at amino acid position 297 to be replaced by a glycine (G). 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	0.21
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	23
DANN	Benign	0.93
DEOGEN2	Benign	0.13	.;T;.;.;T;T
Eigen	Benign	-0.096
Eigen_PC	Benign	0.043
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.59	T;T;T;T;.;T
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.25	T;T;T;T;T;T
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Benign	0.080	N;N;N;.;N;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.090	N;N;N;N;N;N
REVEL	Uncertain	0.42
Sift	Benign	0.40	T;T;T;T;T;T
Sift4G	Benign	0.38	T;T;T;T;T;T
Polyphen		0.27	B;B;.;.;B;.
Vest4		0.32
MutPred		0.55		Loss of stability (P = 0.0038);Loss of stability (P = 0.0038);Loss of stability (P = 0.0038);.;Loss of stability (P = 0.0038);.;
MVP		0.88
MPC		0.37
ClinPred		0.30	T
GERP RS		4.7
Varity_R		0.12
gMVP		0.63

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: rs1811315895; hg19: chr8-98973690;