Variant 9-130299289-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 3P and 6B. PVS1_ModeratePP3BP6_ModerateBS2

The NM_001291815.2(HMCN2):c.1276+1G>A variant causes a splice donor, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 451,704 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 3 hom. )

Consequence

HMCN2
NM_001291815.2 splice_donor, intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.67

Variant links:

Genes affected

HMCN2 (HGNC:21293): (hemicentin 2) Predicted to enable calcium ion binding activity. Predicted to be an extracellular matrix structural constituent. Predicted to be involved in cell adhesion. Located in collagen-containing extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

HMCN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.017257217 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.

PP3

Multiple lines of computational evidence support a deleterious effect 4: BayesDel_noAF, Cadd, Eigen, phyloP100way_vertebrate [when BayesDel_addAF was below the threshold]

BP6

Variant 9-130299289-G-A is Benign according to our data. Variant chr9-130299289-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2659581.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMCN2	NM_001291815.2 linkuse as main transcript	c.1276+1G>A		splice_donor_variant, intron_variant		ENST00000683500.2	NP_001278744.1	A0A804HLC3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMCN2	ENST00000683500.2 linkuse as main transcript	c.1276+1G>A		splice_donor_variant, intron_variant			NM_001291815.2	ENSP00000508292.2		A0A804HLC3
HMCN2	ENST00000624552.4 linkuse as main transcript	c.1276+1G>A		splice_donor_variant, intron_variant		5		ENSP00000485357.2		Q8NDA2

Frequencies

GnomAD3 genomes

AF:

0.000789

AC:

120

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00104

AC:

146

AN:

140422

Hom.:

AF XY:

0.000942

AC XY:

AN XY:

75404

show subpopulations

Gnomad AFR exome

AF:

0.000599

Gnomad AMR exome

AF:

0.000607

Gnomad ASJ exome

AF:

0.000795

Gnomad EAS exome

AF:

0.0000945

Gnomad SAS exome

AF:

0.000340

Gnomad FIN exome

AF:

0.000304

Gnomad NFE exome

AF:

0.00186

Gnomad OTH exome

AF:

0.00322

GnomAD4 exome

AF:

0.00116

AC:

347

AN:

299406

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

177

AN XY:

167176

show subpopulations

Gnomad4 AFR exome

AF:

0.000247

Gnomad4 AMR exome

AF:

0.000740

Gnomad4 ASJ exome

AF:

0.000898

Gnomad4 EAS exome

AF:

0.000113

Gnomad4 SAS exome

AF:

0.000362

Gnomad4 FIN exome

AF:

0.000187

Gnomad4 NFE exome

AF:

0.00180

Gnomad4 OTH exome

AF:

0.00113

GnomAD4 genome

AF:

0.000788

AC:

120

AN:

152298

Hom.:

Cov.:

AF XY:

0.000712

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00139

Hom.:

Bravo

AF:

0.000835

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000778

AC:

ExAC

AF:

0.000630

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2023

HMCN2: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.037

BayesDel_noAF

Pathogenic

0.16

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Benign

0.33

GERP RS

4.2

Splicing

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