2-19994065-A-G

Position:

• chr2-19994065-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_002381.5(MATN3):​c.1405+234T>C variant causes a intron change. The variant allele was found at a frequency of 0.0989 in 152,246 control chromosomes in the GnomAD database, including 820 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.099 (820 hom., cov: 32)
• Consequence: MATN3 NM_002381.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.42

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]

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 2-19994065-A-G is Benign according to our data. Variant chr2-19994065-A-G is described in ClinVar as [Benign]. Clinvar id is 1273770.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MATN3	NM_002381.5	c.1405+234T>C		intron_variant		ENST00000407540.8
WDR35-DT	NR_110235.1	n.291+3571A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MATN3	ENST00000407540.8	c.1405+234T>C		intron_variant		1	NM_002381.5	P1
MATN3	ENST00000421259.2	c.1279+234T>C		intron_variant		1
WDR35-DT	ENST00000416575.2	n.284+3571A>G		intron_variant, non_coding_transcript_variant		2
WDR35-DT	ENST00000658200.1	n.286+3571A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0989 AC: 15050 AN: 152128 Hom.: 816 Cov.: 32

Gnomad AFR AF: 0.0716

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0854

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.0923

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.0989 AC: 15053 AN: 152246 Hom.: 820 Cov.: 32 AF XY: 0.100 AC XY: 7447 AN XY: 74448

Gnomad4 AFR AF: 0.0715

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.0854

Gnomad4 EAS AF: 0.230

Gnomad4 SAS AF: 0.177

Gnomad4 FIN AF: 0.0923

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.108

Alfa AF: 0.0983 Hom.: 154

Bravo AF: 0.0963

Asia WGS AF: 0.238 AC: 829 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	14
DANN	Benign	0.90

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: rs55919320; hg19: chr2-20193826;