8-97941780-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_002380.5(MATN2):c.716C>T(p.Ala239Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000347 in 1,439,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: MATN2 NM_002380.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.199

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049256474).
• BP6: Variant 8-97941780-C-T is Benign according to our data. Variant chr8-97941780-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2270220.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MATN2	NM_002380.5	c.716C>T	p.Ala239Val	missense_variant	4/19	ENST00000254898.7
MATN2	NM_030583.4	c.716C>T	p.Ala239Val	missense_variant	4/19
MATN2	NM_001317748.2	c.716C>T	p.Ala239Val	missense_variant	4/18
MATN2	XM_005250920.3	c.716C>T	p.Ala239Val	missense_variant	4/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MATN2	ENST00000254898.7	c.716C>T	p.Ala239Val	missense_variant	4/19	1	NM_002380.5	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000922 AC: 2 AN: 217018 Hom.: 0 AF XY: 0.00000857 AC XY: 1 AN XY: 116732

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.0000207

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000347 AC: 5 AN: 1439416 Hom.: 0 Cov.: 29 AF XY: 0.00000700 AC XY: 5 AN XY: 713988

Gnomad4 AFR exome AF: 0.0000302

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: 0.00000363

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000611 Hom.: 0

ExAC AF: 0.0000331 AC: 4

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 05, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.39
Cadd	Benign	4.1
Dann	Benign	0.51
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.52	T;T;T;.
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.049	T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-1.6	N;N;N;N
MutationTaster	Benign	1.0	D;N;N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.67	N;N;N;N
REVEL	Benign	0.17
Sift	Benign	0.55	T;T;T;T
Sift4G	Benign	0.51	T;T;T;T
Polyphen		0.0	B;B;.;B
Vest4		0.046
MVP		0.72
MPC		0.19
ClinPred		0.049	T
GERP RS		-0.016
Varity_R		0.019
gMVP		0.54

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: rs765400588; hg19: chr8-98954008;