8-97994561-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_002380.5(MATN2):c.1163T>C(p.Leu388Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000954 in 1,613,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000094 ( 0 hom. )
Consequence
MATN2
NM_002380.5 missense
NM_002380.5 missense
Scores
8
10
Clinical Significance
Conservation
PhyloP100: 1.59
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 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.26060647).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MATN2 | NM_002380.5 | c.1163T>C | p.Leu388Pro | missense_variant | 7/19 | ENST00000254898.7 | |
MATN2 | NM_030583.4 | c.1163T>C | p.Leu388Pro | missense_variant | 7/19 | ||
MATN2 | XM_005250920.3 | c.1163T>C | p.Leu388Pro | missense_variant | 7/18 | ||
MATN2 | NM_001317748.2 | c.1082-9100T>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MATN2 | ENST00000254898.7 | c.1163T>C | p.Leu388Pro | missense_variant | 7/19 | 1 | NM_002380.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000112 AC: 17AN: 152236Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000402 AC: 10AN: 248906Hom.: 0 AF XY: 0.0000518 AC XY: 7AN XY: 135036
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GnomAD4 exome AF: 0.0000937 AC: 137AN: 1461364Hom.: 0 Cov.: 32 AF XY: 0.0000784 AC XY: 57AN XY: 726960
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GnomAD4 genome ? AF: 0.000112 AC: 17AN: 152236Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74378
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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 | May 09, 2023 | The c.1163T>C (p.L388P) alteration is located in exon 7 (coding exon 6) of the MATN2 gene. This alteration results from a T to C substitution at nucleotide position 1163, causing the leucine (L) at amino acid position 388 to be replaced by a proline (P). 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
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;D;.;T;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
N;N;.;N;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;N;N
REVEL
Uncertain
Sift
Benign
T;T;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T
Polyphen
P;D;.;D;.;.
Vest4
MVP
MPC
0.34
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