Variant 2-19994275-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002381.5(MATN3):c.1405+24C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 1,522,864 control chromosomes in the GnomAD database, including 153,781 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16044 hom., cov: 33)

Exomes 𝑓: 0.44 ( 137737 hom. )

Consequence

MATN3
NM_002381.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.171

Variant links:

Genes affected

MATN3 (HGNC:6909): (matrilin 3) This gene encodes a member of 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 two von Willebrand factor A domains; it is present in the cartilage extracellular matrix and has a role in the development and homeostasis of cartilage and bone. Mutations in this gene result in multiple epiphyseal dysplasia. [provided by RefSeq, Jul 2008]

MATN3 links:

WDR35-DT (HGNC:55818): (WDR35 divergent transcript)

WDR35-DT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 2-19994275-G-C is Benign according to our data. Variant chr2-19994275-G-C is described in ClinVar as [Benign]. Clinvar id is 258646.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MATN3	NM_002381.5 linkuse as main transcript	c.1405+24C>G		intron_variant		ENST00000407540.8
WDR35-DT	NR_110235.1 linkuse as main transcript	n.291+3781G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
MATN3	ENST00000407540.8 linkuse as main transcript	c.1405+24C>G	intron_variant	1	NM_002381.5	P1	O15232-1
MATN3	ENST00000421259.2 linkuse as main transcript	c.1279+24C>G	intron_variant	1			O15232-2
WDR35-DT	ENST00000416575.2 linkuse as main transcript	n.284+3781G>C	intron_variant, non_coding_transcript_variant	2
WDR35-DT	ENST00000658200.1 linkuse as main transcript	n.286+3781G>C	intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.456

AC:

69280

AN:

151898

Hom.:

16020

Cov.:

show subpopulations

Gnomad AFR

AF:

0.469

Gnomad AMI

AF:

0.533

Gnomad AMR

AF:

0.491

Gnomad ASJ

AF:

0.408

Gnomad EAS

AF:

0.639

Gnomad SAS

AF:

0.589

Gnomad FIN

AF:

0.431

Gnomad MID

AF:

0.421

Gnomad NFE

AF:

0.422

Gnomad OTH

AF:

0.466

GnomAD3 exomes

AF:

0.473

AC:

108917

AN:

230198

Hom.:

26298

AF XY:

0.476

AC XY:

59198

AN XY:

124350

show subpopulations

Gnomad AFR exome

AF:

0.468

Gnomad AMR exome

AF:

0.493

Gnomad ASJ exome

AF:

0.416

Gnomad EAS exome

AF:

0.635

Gnomad SAS exome

AF:

0.596

Gnomad FIN exome

AF:

0.436

Gnomad NFE exome

AF:

0.420

Gnomad OTH exome

AF:

0.469

GnomAD4 exome

AF:

0.443

AC:

607377

AN:

1370848

Hom.:

137737

Cov.:

AF XY:

0.447

AC XY:

306248

AN XY:

685226

show subpopulations

Gnomad4 AFR exome

AF:

0.473

Gnomad4 AMR exome

AF:

0.486

Gnomad4 ASJ exome

AF:

0.422

Gnomad4 EAS exome

AF:

0.698

Gnomad4 SAS exome

AF:

0.591

Gnomad4 FIN exome

AF:

0.431

Gnomad4 NFE exome

AF:

0.419

Gnomad4 OTH exome

AF:

0.448

GnomAD4 genome

AF:

0.456

AC:

69355

AN:

152016

Hom.:

16044

Cov.:

AF XY:

0.461

AC XY:

34282

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.469

Gnomad4 AMR

AF:

0.492

Gnomad4 ASJ

AF:

0.408

Gnomad4 EAS

AF:

0.638

Gnomad4 SAS

AF:

0.587

Gnomad4 FIN

AF:

0.431

Gnomad4 NFE

AF:

0.422

Gnomad4 OTH

AF:

0.473

Alfa

AF:

0.437

Hom.:

2674

Bravo

AF:

0.456

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over