8-98030470-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002380.5(MATN2):​c.2365A>G​(p.Met789Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,613,142 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: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

MATN2
NM_002380.5 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.15
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.25135484).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MATN2NM_002380.5 linkc.2365A>G p.Met789Val missense_variant Exon 15 of 19 ENST00000254898.7 NP_002371.3 O00339-1A0A140VKH7Q8N2G3
MATN2NM_030583.4 linkc.2365A>G p.Met789Val missense_variant Exon 15 of 19 NP_085072.2 O00339-2Q8N2G3
MATN2NM_001317748.2 linkc.2242A>G p.Met748Val missense_variant Exon 14 of 18 NP_001304677.1 O00339-3Q8N2G3
MATN2XM_005250920.3 linkc.1951A>G p.Met651Val missense_variant Exon 14 of 18 XP_005250977.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MATN2ENST00000254898.7 linkc.2365A>G p.Met789Val missense_variant Exon 15 of 19 1 NM_002380.5 ENSP00000254898.6 O00339-1
MATN2ENST00000520016.5 linkc.2365A>G p.Met789Val missense_variant Exon 14 of 18 1 ENSP00000430487.1 O00339-1
MATN2ENST00000521689.5 linkc.2365A>G p.Met789Val missense_variant Exon 15 of 19 1 ENSP00000429977.1 O00339-2
MATN2ENST00000524308.5 linkc.2242A>G p.Met748Val missense_variant Exon 14 of 18 1 ENSP00000430221.1 O00339-3
MATN2ENST00000518154.5 linkc.1711A>G p.Met571Val missense_variant Exon 12 of 16 1 ENSP00000429622.1 H0YBJ4
MATN2ENST00000522025.6 linkc.1513A>G p.Met505Val missense_variant Exon 14 of 18 5 ENSP00000429010.1 O00339-4
MATN2ENST00000521952.5 linkn.*33A>G non_coding_transcript_exon_variant Exon 5 of 9 5 ENSP00000429256.1 H0YBD5
MATN2ENST00000521952.5 linkn.*33A>G 3_prime_UTR_variant Exon 5 of 9 5 ENSP00000429256.1 H0YBD5

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152162
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000807
AC:
2
AN:
247922
Hom.:
0
AF XY:
0.00000743
AC XY:
1
AN XY:
134526
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000112
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:
0.00000342
AC:
5
AN:
1460980
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
726734
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152162
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74336
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.00000828
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 22, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2365A>G (p.M789V) alteration is located in exon 15 (coding exon 14) of the MATN2 gene. This alteration results from a A to G substitution at nucleotide position 2365, causing the methionine (M) at amino acid position 789 to be replaced by a valine (V). 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
0.080
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.24
CADD
Benign
18
DANN
Benign
0.96
DEOGEN2
Benign
0.11
.;T;.;.;T
Eigen
Benign
-0.14
Eigen_PC
Benign
-0.10
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.73
T;T;T;T;.
M_CAP
Benign
0.027
D
MetaRNN
Benign
0.25
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.60
N;N;.;.;N
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-1.2
N;N;N;N;N
REVEL
Benign
0.22
Sift
Uncertain
0.021
D;D;D;D;D
Sift4G
Uncertain
0.054
T;T;T;T;T
Polyphen
0.0010
B;B;.;.;B
Vest4
0.18
MutPred
0.57
Loss of MoRF binding (P = 0.1057);Loss of MoRF binding (P = 0.1057);.;.;Loss of MoRF binding (P = 0.1057);
MVP
0.86
MPC
0.20
ClinPred
0.22
T
GERP RS
1.6
Varity_R
0.11
gMVP
0.56

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs780408664; hg19: chr8-99042698; API