8-98033053-G-C

Variant names:

• chr8-98033053-G-C
• NM_002380.5:c.2593G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002380.5(MATN2):​c.2593G>C​(p.Val865Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,454,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MATN2 NM_002380.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.563

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:10333): (ribosomal protein L30) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L30E family of ribosomal proteins. It is located in the cytoplasm. This gene is co-transcribed with the U72 small nucleolar RNA gene, which is located in its fourth intron. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

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=0.10763964).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MATN2	NM_002380.5	c.2593G>C	p.Val865Leu	missense_variant	Exon 17 of 19	ENST00000254898.7	NP_002371.3
MATN2	NM_001317748.2	c.2470G>C	p.Val824Leu	missense_variant	Exon 16 of 18		NP_001304677.1
MATN2	XM_005250920.3	c.2179G>C	p.Val727Leu	missense_variant	Exon 16 of 18		XP_005250977.1
MATN2	NM_030583.4	c.2582-46G>C		intron_variant	Intron 16 of 18		NP_085072.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MATN2	ENST00000254898.7	c.2593G>C	p.Val865Leu	missense_variant	Exon 17 of 19	1	NM_002380.5	ENSP00000254898.6
MATN2	ENST00000520016.5	c.2593G>C	p.Val865Leu	missense_variant	Exon 16 of 18	1		ENSP00000430487.1
MATN2	ENST00000524308.5	c.2470G>C	p.Val824Leu	missense_variant	Exon 16 of 18	1		ENSP00000430221.1
MATN2	ENST00000522025.6	c.1741G>C	p.Val581Leu	missense_variant	Exon 16 of 18	5		ENSP00000429010.1
MATN2	ENST00000521689.5	c.2582-46G>C		intron_variant	Intron 16 of 18	1		ENSP00000429977.1
MATN2	ENST00000518154.5	c.1928-46G>C		intron_variant	Intron 13 of 15	1		ENSP00000429622.1
MATN2	ENST00000521952.5	n.*261G>C		non_coding_transcript_exon_variant	Exon 7 of 9	5		ENSP00000429256.1
MATN2	ENST00000521952.5	n.*261G>C		3_prime_UTR_variant	Exon 7 of 9	5		ENSP00000429256.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1454420 Hom.: 0 Cov.: 31 AF XY: 0.00000277 AC XY: 2 AN XY: 723138

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: 0.00000180

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

Jan 27, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2593G>C (p.V865L) alteration is located in exon 17 (coding exon 16) of the MATN2 gene. This alteration results from a G to C substitution at nucleotide position 2593, causing the valine (V) at amino acid position 865 to be replaced by a leucine (L). 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	0.10
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.019	T;.;.;T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.33
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.74	T;T;T;.
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	0.90	L;.;.;L
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.36	N;N;N;N
REVEL	Benign	0.15
Sift	Benign	0.098	T;T;T;T
Sift4G	Benign	0.33	T;T;T;T
Polyphen		0.079	B;.;.;B
Vest4		0.17
MutPred		0.17		Gain of loop (P = 0.1069);.;.;Gain of loop (P = 0.1069);
MVP		0.80
MPC		0.19
ClinPred		0.11	T
GERP RS		3.0
Varity_R		0.046
gMVP		0.30

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: chr8-99045281;