8-97931055-A-T

Position:

• chr8-97931055-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_002380.5(MATN2):​c.245A>T​(p.Asp82Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MATN2 NM_002380.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.98

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]

MATN2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.753

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MATN2	NM_002380.5	c.245A>T	p.Asp82Val	missense_variant	3/19	ENST00000254898.7	NP_002371.3
MATN2	NM_030583.4	c.245A>T	p.Asp82Val	missense_variant	3/19		NP_085072.2
MATN2	NM_001317748.2	c.245A>T	p.Asp82Val	missense_variant	3/18		NP_001304677.1
MATN2	XM_005250920.3	c.245A>T	p.Asp82Val	missense_variant	3/18		XP_005250977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MATN2	ENST00000254898.7	c.245A>T	p.Asp82Val	missense_variant	3/19	1	NM_002380.5	ENSP00000254898.6
MATN2	ENST00000520016.5	c.245A>T	p.Asp82Val	missense_variant	2/18	1		ENSP00000430487.1
MATN2	ENST00000521689.5	c.245A>T	p.Asp82Val	missense_variant	3/19	1		ENSP00000429977.1
MATN2	ENST00000524308.5	c.245A>T	p.Asp82Val	missense_variant	3/18	1		ENSP00000430221.1
MATN2	ENST00000522025.6	c.-115+515A>T		intron_variant		5		ENSP00000429010.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461682 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727126

Gnomad4 AFR exome AF: 0.0000896

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Jan 02, 2024

The c.245A>T (p.D82V) 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 245, causing the aspartic acid (D) at amino acid position 82 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	Uncertain	0.42
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	.;T;.;T
Eigen	Benign	0.18
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.96	D;D;D;.
M_CAP	Uncertain	0.23	D
MetaRNN	Pathogenic	0.75	D;D;D;D
MetaSVM	Uncertain	0.010	D
MutationAssessor	Uncertain	2.2	M;M;M;M
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-4.2	D;D;D;D
REVEL	Pathogenic	0.70
Sift	Benign	0.043	D;D;D;D
Sift4G	Uncertain	0.030	D;D;D;D
Polyphen		0.38	B;P;.;P
Vest4		0.54
MutPred		0.56		Gain of methylation at K77 (P = 0.1034);Gain of methylation at K77 (P = 0.1034);Gain of methylation at K77 (P = 0.1034);Gain of methylation at K77 (P = 0.1034);
MVP		0.94
MPC		0.42
ClinPred		0.88	D
GERP RS		3.4
Varity_R		0.31
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

LitVar

Other links and lift over

dbSNP: rs765802052; hg19: chr8-98943283;