chr8-98007159-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_002380.5(MATN2):c.1382C>T(p.Thr461Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000694 in 1,613,622 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000068 ( 0 hom. )
Consequence
MATN2
NM_002380.5 missense
NM_002380.5 missense
Scores
9
5
4
Clinical Significance
Conservation
PhyloP100: 3.76
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]
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ACMG classification
Classification made for transcript
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 | UniProt |
---|---|---|---|---|---|---|---|
MATN2 | NM_002380.5 | c.1382C>T | p.Thr461Met | missense_variant | 9/19 | ENST00000254898.7 | |
MATN2 | NM_030583.4 | c.1382C>T | p.Thr461Met | missense_variant | 9/19 | ||
MATN2 | NM_001317748.2 | c.1259C>T | p.Thr420Met | missense_variant | 8/18 | ||
MATN2 | XM_005250920.3 | c.1382C>T | p.Thr461Met | missense_variant | 9/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MATN2 | ENST00000254898.7 | c.1382C>T | p.Thr461Met | missense_variant | 9/19 | 1 | NM_002380.5 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152194Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000604 AC: 15AN: 248196Hom.: 0 AF XY: 0.0000668 AC XY: 9AN XY: 134674
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GnomAD4 exome AF: 0.0000677 AC: 99AN: 1461312Hom.: 0 Cov.: 31 AF XY: 0.0000784 AC XY: 57AN XY: 726906
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GnomAD4 genome AF: 0.0000854 AC: 13AN: 152310Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5AN XY: 74476
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 16, 2024 | The c.1382C>T (p.T461M) alteration is located in exon 9 (coding exon 8) of the MATN2 gene. This alteration results from a C to T substitution at nucleotide position 1382, causing the threonine (T) at amino acid position 461 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T;.;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
M;M;.;.;M;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;D;N;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D
Polyphen
D;D;.;.;D;.
Vest4
MVP
MPC
0.50
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at