8-98027427-G-A

Position:

• chr8-98027427-G-A

Variant summary

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

The NM_002380.5(MATN2):​c.1954G>A​(p.Gly652Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000689 in 1,450,872 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MATN2 NM_002380.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.38

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]

RPL30 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MATN2	NM_002380.5	c.1954G>A	p.Gly652Ser	missense_variant	14/19	ENST00000254898.7	NP_002371.3
MATN2	NM_030583.4	c.1954G>A	p.Gly652Ser	missense_variant	14/19		NP_085072.2
MATN2	NM_001317748.2	c.1831G>A	p.Gly611Ser	missense_variant	13/18		NP_001304677.1
MATN2	XM_005250920.3	c.1943-3035G>A		intron_variant			XP_005250977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MATN2	ENST00000254898.7	c.1954G>A	p.Gly652Ser	missense_variant	14/19	1	NM_002380.5	ENSP00000254898.6
MATN2	ENST00000520016.5	c.1954G>A	p.Gly652Ser	missense_variant	13/18	1		ENSP00000430487.1
MATN2	ENST00000521689.5	c.1954G>A	p.Gly652Ser	missense_variant	14/19	1		ENSP00000429977.1
MATN2	ENST00000524308.5	c.1831G>A	p.Gly611Ser	missense_variant	13/18	1		ENSP00000430221.1
MATN2	ENST00000518154.5	c.1300G>A	p.Gly434Ser	missense_variant	11/16	1		ENSP00000429622.1
MATN2	ENST00000522025.6	c.1102G>A	p.Gly368Ser	missense_variant	13/18	5		ENSP00000429010.1
MATN2	ENST00000521952.5	n.*25-3035G>A		intron_variant		5		ENSP00000429256.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1450872 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 719380

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: 0.00

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 32

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

Oct 23, 2024

The c.1954G>A (p.G652S) alteration is located in exon 14 (coding exon 13) of the MATN2 gene. This alteration results from a G to A substitution at nucleotide position 1954, causing the glycine (G) at amino acid position 652 to be replaced by a serine (S). 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	0.22
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.075	.;T;.;.;T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D;D;D;.
M_CAP	Benign	0.061	D
MetaRNN	Uncertain	0.61	D;D;D;D;D
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	1.8	L;L;.;.;L
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.8	N;N;N;N;N
REVEL	Uncertain	0.49
Sift	Benign	0.092	T;T;T;T;T
Sift4G	Benign	0.20	T;T;T;T;T
Polyphen		1.0	D;D;.;.;D
Vest4		0.62
MutPred		0.37		Gain of phosphorylation at G652 (P = 0.0851);Gain of phosphorylation at G652 (P = 0.0851);.;.;Gain of phosphorylation at G652 (P = 0.0851);
MVP		0.97
MPC		0.35
ClinPred		0.98	D
GERP RS		5.1
Varity_R		0.49
gMVP		0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr8-99039655;