8-97931303-A-T

Position:

• chr8-97931303-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002380.5(MATN2):​c.493A>T​(p.Ile165Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MATN2 NM_002380.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.02

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36534077).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MATN2	NM_002380.5	c.493A>T	p.Ile165Leu	missense_variant	3/19	ENST00000254898.7
MATN2	NM_030583.4	c.493A>T	p.Ile165Leu	missense_variant	3/19
MATN2	NM_001317748.2	c.493A>T	p.Ile165Leu	missense_variant	3/18
MATN2	XM_005250920.3	c.493A>T	p.Ile165Leu	missense_variant	3/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MATN2	ENST00000254898.7	c.493A>T	p.Ile165Leu	missense_variant	3/19	1	NM_002380.5	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

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

Apr 06, 2023

The c.493A>T (p.I165L) alteration is located in exon 3 (coding exon 2) of the MATN2 gene. This alteration results from a A to T substitution at nucleotide position 493, causing the isoleucine (I) at amino acid position 165 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	0.20
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	23
DANN	Uncertain	0.99
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.90	D;D;T;.
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.37	T;T;T;T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	-0.26	N;N;N;N
MutationTaster	Benign	0.94	D;D;D;D;D
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.57	N;N;N;N
REVEL	Uncertain	0.35
Sift	Benign	0.13	T;T;T;T
Sift4G	Benign	0.11	T;T;T;T
Polyphen		0.93	P;D;.;D
Vest4		0.35
MutPred		0.66		Gain of catalytic residue at I165 (P = 0.1086);Gain of catalytic residue at I165 (P = 0.1086);Gain of catalytic residue at I165 (P = 0.1086);Gain of catalytic residue at I165 (P = 0.1086);
MVP		0.87
MPC		0.20
ClinPred		0.94	D
GERP RS		4.8
Varity_R		0.14
gMVP		0.75

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-98943531;