rs4077920

chr8-97881636-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002380.5(MATN2):c.-26-6439A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.843 in 152,162 control chromosomes in the GnomAD database, including 54,866 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.84 (54866 hom., cov: 33)
• Consequence: MATN2 NM_002380.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.353

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MATN2	NM_002380.5	c.-26-6439A>C		intron_variant		ENST00000254898.7
MATN2	NM_001317748.2	c.-26-6439A>C		intron_variant
MATN2	NM_030583.4	c.-26-6439A>C		intron_variant
MATN2	XM_005250920.3	c.-26-6439A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MATN2	ENST00000254898.7	c.-26-6439A>C		intron_variant		1	NM_002380.5	P4

Frequencies

GnomAD3 genomes AF: 0.843 AC: 128164 AN: 152042 Hom.: 54839 Cov.: 33

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.914

Gnomad AMR AF: 0.844

Gnomad ASJ AF: 0.904

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.831

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.934

Gnomad OTH AF: 0.855

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.843 AC: 128240 AN: 152162 Hom.: 54866 Cov.: 33 AF XY: 0.835 AC XY: 62089 AN XY: 74402

Gnomad4 AFR AF: 0.725

Gnomad4 AMR AF: 0.843

Gnomad4 ASJ AF: 0.904

Gnomad4 EAS AF: 0.633

Gnomad4 SAS AF: 0.764

Gnomad4 FIN AF: 0.831

Gnomad4 NFE AF: 0.934

Gnomad4 OTH AF: 0.851

Alfa AF: 0.914 Hom.: 129878

Bravo AF: 0.838

Asia WGS AF: 0.697 AC: 2426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	3.6
Dann	Benign	0.81

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: rs4077920; hg19: chr8-98893864;