8-97941780-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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. 17/22 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
• 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: Likely_benign. The variant received -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 VariationId is 2270220.Status of the report is criteria_provided_single_submitter, 1 stars.

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>T	p.Ala239Val	missense	Exon 4 of 19	NP_002371.3
	MATN2	NM_030583.4		c.716C>T	p.Ala239Val	missense	Exon 4 of 19	NP_085072.2	O00339-2
	MATN2	NM_001317748.2		c.716C>T	p.Ala239Val	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>T	p.Ala239Val	missense	Exon 4 of 19	ENSP00000254898.6	O00339-1
	MATN2	ENST00000520016.5	TSL:1	c.716C>T	p.Ala239Val	missense	Exon 3 of 18	ENSP00000430487.1	O00339-1
	MATN2	ENST00000521689.5	TSL:1	c.716C>T	p.Ala239Val	missense	Exon 4 of 19	ENSP00000429977.1	O00339-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000922 AC: 2 AN: 217018 AF XY: 0.00000857

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 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

African (AFR) AF: 0.0000302 AC: 1 AN: 33138

American (AMR) AF: 0.00 AC: 0 AN: 40206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25650

East Asian (EAS) AF: 0.00 AC: 0 AN: 38822

South Asian (SAS) AF: 0.00 AC: 0 AN: 82930

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 0.00000363 AC: 4 AN: 1100960

Other (OTH) AF: 0.00 AC: 0 AN: 59716

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000611 Hom.: 0

ExAC AF: 0.0000331 AC: 4

ClinVar

ClinVar submissions

Significance: Likely benign

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	Benign	0.069
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	4.1
DANN	Benign	0.51
DEOGEN2	Benign	0.022	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-1.6	N
PhyloP100		0.20
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.67	N
REVEL	Benign	0.17
Sift	Benign	0.55	T
Sift4G	Benign	0.51	T
Polyphen		0.0	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
Mutation Taster		=97/3	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;