rs765400588

Variant names:

• chr8-97941780-C-A
• rs765400588
• NM_002380.5:c.716C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-97941780-C-A
• chr8-97941780-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002380.5(MATN2):​c.716C>A​(p.Ala239Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A239V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MATN2 NM_002380.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.199
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13744864).

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.716C>A	p.Ala239Asp	missense	Exon 4 of 19	NP_002371.3
	MATN2	NM_030583.4		c.716C>A	p.Ala239Asp	missense	Exon 4 of 19	NP_085072.2	O00339-2
	MATN2	NM_001317748.2		c.716C>A	p.Ala239Asp	missense	Exon 4 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.716C>A	p.Ala239Asp	missense	Exon 4 of 19	ENSP00000254898.6	O00339-1
	MATN2	ENST00000520016.5	TSL:1	c.716C>A	p.Ala239Asp	missense	Exon 3 of 18	ENSP00000430487.1	O00339-1
	MATN2	ENST00000521689.5	TSL:1	c.716C>A	p.Ala239Asp	missense	Exon 4 of 19	ENSP00000429977.1	O00339-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	5.2
DANN	Benign	0.95
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.071	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.41	N
PhyloP100		0.20
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.12
Sift	Benign	0.60	T
Sift4G	Benign	0.61	T
Polyphen		0.13	B
Vest4		0.24
MutPred		0.41		Gain of ubiquitination at K235 (P = 0.0579)
MVP		0.84
MPC		0.33
ClinPred		0.077	T
GERP RS		-0.016
Varity_R		0.10
gMVP		0.78
Mutation Taster		=94/6	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: rs765400588; hg19: chr8-98954008;