8-97931300-G-C

Variant names:

• chr8-97931300-G-C
• rs1391103453
• NM_002380.5:c.490G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002380.5(MATN2):​c.490G>C​(p.Val164Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,620 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MATN2 NM_002380.5 missense
• Clinical Significance: Not reported in ClinVar
• 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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.864

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MATN2	NM_002380.5	c.490G>C	p.Val164Leu	missense_variant	Exon 3 of 19	ENST00000254898.7	NP_002371.3
MATN2	NM_030583.4	c.490G>C	p.Val164Leu	missense_variant	Exon 3 of 19		NP_085072.2
MATN2	NM_001317748.2	c.490G>C	p.Val164Leu	missense_variant	Exon 3 of 18		NP_001304677.1
MATN2	XM_005250920.3	c.490G>C	p.Val164Leu	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.490G>C	p.Val164Leu	missense_variant	Exon 3 of 19	1	NM_002380.5	ENSP00000254898.6
MATN2	ENST00000520016.5	c.490G>C	p.Val164Leu	missense_variant	Exon 2 of 18	1		ENSP00000430487.1
MATN2	ENST00000521689.5	c.490G>C	p.Val164Leu	missense_variant	Exon 3 of 19	1		ENSP00000429977.1
MATN2	ENST00000524308.5	c.490G>C	p.Val164Leu	missense_variant	Exon 3 of 18	1		ENSP00000430221.1
MATN2	ENST00000522025.6	c.-115+760G>C		intron_variant	Intron 2 of 17	5		ENSP00000429010.1
MATN2	ENST00000518154.5	c.-42G>C		upstream_gene_variant		1		ENSP00000429622.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248716 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134928

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461620 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 727088

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.13
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	.;T;.;T
Eigen	Benign	0.11
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.96	D;D;D;.
M_CAP	Benign	0.082	D
MetaRNN	Pathogenic	0.86	D;D;D;D
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Benign	1.9	M;M;M;M
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-2.2	N;N;N;N
REVEL	Uncertain	0.60
Sift	Uncertain	0.0020	D;D;D;D
Sift4G	Uncertain	0.0050	D;D;D;D
Polyphen		0.052	B;B;.;B
Vest4		0.49
MutPred		0.91		Loss of MoRF binding (P = 0.2975);Loss of MoRF binding (P = 0.2975);Loss of MoRF binding (P = 0.2975);Loss of MoRF binding (P = 0.2975);
MVP		0.93
MPC		0.37
ClinPred		0.65	D
GERP RS		3.9
Varity_R		0.36
gMVP		0.68

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: rs1391103453; hg19: chr8-98943528;