chr8-97931134-G-C

Variant names:

• chr8-97931134-G-C
• rs200323821
• NM_002380.5:c.324G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_002380.5(MATN2):​c.324G>C​(p.Glu108Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000437 in 1,614,018 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00046 (1 hom.)
• Consequence: MATN2 NM_002380.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.56
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.795

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002380.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MATN2	NM_002380.5	MANE Select	c.324G>C	p.Glu108Asp	missense	Exon 3 of 19	NP_002371.3
	MATN2	NM_030583.4		c.324G>C	p.Glu108Asp	missense	Exon 3 of 19	NP_085072.2	O00339-2
	MATN2	NM_001317748.2		c.324G>C	p.Glu108Asp	missense	Exon 3 of 18	NP_001304677.1	O00339-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MATN2	ENST00000254898.7	TSL:1 MANE Select	c.324G>C	p.Glu108Asp	missense	Exon 3 of 19	ENSP00000254898.6	O00339-1
	MATN2	ENST00000520016.5	TSL:1	c.324G>C	p.Glu108Asp	missense	Exon 2 of 18	ENSP00000430487.1	O00339-1
	MATN2	ENST00000521689.5	TSL:1	c.324G>C	p.Glu108Asp	missense	Exon 3 of 19	ENSP00000429977.1	O00339-2

Frequencies

GnomAD3 genomes AF: 0.000230 AC: 35 AN: 152212 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000245 AC: 61 AN: 248940 AF XY: 0.000215

Gnomad AFR exome AF: 0.000258

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000488

Gnomad OTH exome AF: 0.000331

GnomAD4 exome AF: 0.000459 AC: 671 AN: 1461688 Hom.: 1 Cov.: 30 AF XY: 0.000425 AC XY: 309 AN XY: 727124

African (AFR) AF: 0.000209 AC: 7 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.000112 AC: 6 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000580 AC: 645 AN: 1111852

Other (OTH) AF: 0.000215 AC: 13 AN: 60374

GnomAD4 genome AF: 0.000230 AC: 35 AN: 152330 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74486

African (AFR) AF: 0.0000962 AC: 4 AN: 41570

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000456 AC: 31 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000365 Hom.: 0

Bravo AF: 0.000238

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000718 AC: 3

ESP6500EA AF: 0.000472 AC: 4

ExAC AF: 0.000339 AC: 41

EpiCase AF: 0.000273

EpiControl AF: 0.000533

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Uncertain	0.47	D
MutationAssessor	Pathogenic	3.1	M
PhyloP100		2.6
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.62
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.93
MutPred		0.66		Gain of MoRF binding (P = 0.0992)
MVP		0.89
MPC		0.72
ClinPred		0.15	T
GERP RS		1.9
PromoterAI		0.0083	Neutral
Varity_R		0.56
gMVP		0.72
Mutation Taster		=64/36	polymorphism

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

Other links and lift over

dbSNP: rs200323821; hg19: chr8-98943362;