8-97931078-G-C

Variant names:

• chr8-97931078-G-C
• rs757584045
• NM_002380.5:c.268G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002380.5(MATN2):​c.268G>C​(p.Gly90Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G90S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MATN2 NM_002380.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.08
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002380.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MATN2	NM_002380.5	MANE Select	c.268G>C	p.Gly90Arg	missense	Exon 3 of 19	NP_002371.3
	MATN2	NM_030583.4		c.268G>C	p.Gly90Arg	missense	Exon 3 of 19	NP_085072.2	O00339-2
	MATN2	NM_001317748.2		c.268G>C	p.Gly90Arg	missense	Exon 3 of 18	NP_001304677.1	O00339-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MATN2	ENST00000254898.7	TSL:1 MANE Select	c.268G>C	p.Gly90Arg	missense	Exon 3 of 19	ENSP00000254898.6	O00339-1
	MATN2	ENST00000520016.5	TSL:1	c.268G>C	p.Gly90Arg	missense	Exon 2 of 18	ENSP00000430487.1	O00339-1
	MATN2	ENST00000521689.5	TSL:1	c.268G>C	p.Gly90Arg	missense	Exon 3 of 19	ENSP00000429977.1	O00339-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Uncertain	0.085	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.15	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Uncertain	0.14	D
MutationAssessor	Uncertain	2.6	M
PhyloP100		4.1
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-6.2	D
REVEL	Uncertain	0.56
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.025	D
Polyphen		0.020	B
Vest4		0.42
MutPred		0.78		Loss of stability (P = 0.1562)
MVP		0.91
MPC		0.30
ClinPred		0.88	D
GERP RS		4.8
PromoterAI		0.050	Neutral
Varity_R		0.26
gMVP		0.88
Mutation Taster		=72/28	polymorphism

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

Other links and lift over

dbSNP: rs757584045; hg19: chr8-98943306;