8-98027434-T-C

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002380.5(MATN2):c.1961T>C(p.Ile654Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000186 in 1,453,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

MATN2
NM_002380.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.22

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]

MATN2 links:

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]

RPL30 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.2957354).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MATN2	NM_002380.5 link	c.1961T>C	p.Ile654Thr	missense_variant	Exon 14 of 19	ENST00000254898.7	NP_002371.3	O00339-1A0A140VKH7Q8N2G3
MATN2	NM_030583.4 link	c.1961T>C	p.Ile654Thr	missense_variant	Exon 14 of 19		NP_085072.2	O00339-2Q8N2G3
MATN2	NM_001317748.2 link	c.1838T>C	p.Ile613Thr	missense_variant	Exon 13 of 18		NP_001304677.1	O00339-3Q8N2G3
MATN2	XM_005250920.3 link	c.1943-3028T>C		intron_variant	Intron 13 of 17		XP_005250977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MATN2	ENST00000254898.7 link	c.1961T>C	p.Ile654Thr	missense_variant	Exon 14 of 19	1	NM_002380.5	ENSP00000254898.6	O00339-1
MATN2	ENST00000520016.5 link	c.1961T>C	p.Ile654Thr	missense_variant	Exon 13 of 18	1		ENSP00000430487.1	O00339-1
MATN2	ENST00000521689.5 link	c.1961T>C	p.Ile654Thr	missense_variant	Exon 14 of 19	1		ENSP00000429977.1	O00339-2
MATN2	ENST00000524308.5 link	c.1838T>C	p.Ile613Thr	missense_variant	Exon 13 of 18	1		ENSP00000430221.1	O00339-3
MATN2	ENST00000518154.5 link	c.1307T>C	p.Ile436Thr	missense_variant	Exon 11 of 16	1		ENSP00000429622.1	H0YBJ4
MATN2	ENST00000522025.6 link	c.1109T>C	p.Ile370Thr	missense_variant	Exon 13 of 18	5		ENSP00000429010.1	O00339-4
MATN2	ENST00000521952.5 link	n.*25-3028T>C		intron_variant	Intron 4 of 8	5		ENSP00000429256.1	H0YBD5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000242

AC:

AN:

248248

Hom.:

AF XY:

0.0000297

AC XY:

AN XY:

134676

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000444

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000186

AC:

AN:

1453888

Hom.:

Cov.:

AF XY:

0.0000222

AC XY:

AN XY:

721454

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000208

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000301

Hom.:

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000331

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 28, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1961T>C (p.I654T) alteration is located in exon 14 (coding exon 13) of the MATN2 gene. This alteration results from a T to C substitution at nucleotide position 1961, causing the isoleucine (I) at amino acid position 654 to be replaced by a threonine (T). 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

0.23

BayesDel_addAF

Benign

-0.084

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Benign

0.92

DEOGEN2

Benign

0.061

.;T;.;.;T

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.000040

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.80

T;T;T;T;.

M_CAP

Benign

0.034

MetaRNN

Benign

0.30

T;T;T;T;T

MetaSVM

Benign

-0.62

MutationAssessor

Benign

0.32

N;N;.;.;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-2.1

N;N;N;N;N

REVEL

Benign

0.28

Sift

Benign

0.30

T;T;T;T;T

Sift4G

Benign

0.41

T;T;T;T;T

Polyphen

0.12

B;B;.;.;B

Vest4

0.33

MutPred

0.50

Loss of stability (P = 0.0209);Loss of stability (P = 0.0209);.;.;Loss of stability (P = 0.0209);

MVP

0.85

MPC

0.29

ClinPred

0.19

GERP RS

5.1

Varity_R

0.22

gMVP

0.63

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over