8-97931270-G-C

Variant names:

• chr8-97931270-G-C
• NM_002380.5:c.460G>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.460G>C​(p.Ala154Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,602 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: 9.94

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, 0.903

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MATN2	NM_002380.5	c.460G>C	p.Ala154Pro	missense_variant	Exon 3 of 19	ENST00000254898.7	NP_002371.3
MATN2	NM_030583.4	c.460G>C	p.Ala154Pro	missense_variant	Exon 3 of 19		NP_085072.2
MATN2	NM_001317748.2	c.460G>C	p.Ala154Pro	missense_variant	Exon 3 of 18		NP_001304677.1
MATN2	XM_005250920.3	c.460G>C	p.Ala154Pro	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.460G>C	p.Ala154Pro	missense_variant	Exon 3 of 19	1	NM_002380.5	ENSP00000254898.6
MATN2	ENST00000520016.5	c.460G>C	p.Ala154Pro	missense_variant	Exon 2 of 18	1		ENSP00000430487.1
MATN2	ENST00000521689.5	c.460G>C	p.Ala154Pro	missense_variant	Exon 3 of 19	1		ENSP00000429977.1
MATN2	ENST00000524308.5	c.460G>C	p.Ala154Pro	missense_variant	Exon 3 of 18	1		ENSP00000430221.1
MATN2	ENST00000522025.6	c.-115+730G>C		intron_variant	Intron 2 of 17	5		ENSP00000429010.1
MATN2	ENST00000518154.5	c.-72G>C		upstream_gene_variant		1		ENSP00000429622.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461602 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 727072

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.39
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	.;T;.;T
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	1.0
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;D;D;.
M_CAP	Benign	0.076	D
MetaRNN	Pathogenic	0.90	D;D;D;D
MetaSVM	Uncertain	0.69	D
MutationAssessor	Pathogenic	3.2	M;M;M;M
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-4.1	D;D;D;D
REVEL	Pathogenic	0.71
Sift	Uncertain	0.0020	D;D;D;D
Sift4G	Uncertain	0.014	D;D;D;D
Polyphen		1.0	D;D;.;D
Vest4		0.83
MutPred		0.76		Gain of glycosylation at A154 (P = 0.0776);Gain of glycosylation at A154 (P = 0.0776);Gain of glycosylation at A154 (P = 0.0776);Gain of glycosylation at A154 (P = 0.0776);
MVP		0.97
MPC		0.87
ClinPred		1.0	D
GERP RS		6.0
Varity_R		0.94
gMVP		0.90

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: chr8-98943498;