Variant 9-130410582-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001291815.2(HMCN2):c.12891G>A(p.Ala4297Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00203 in 1,550,556 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0042 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 15 hom. )

Consequence

HMCN2
NM_001291815.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.25

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 Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 9-130410582-G-A is Benign according to our data. Variant chr9-130410582-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2659601.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.25 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMCN2	NM_001291815.2 linkuse as main transcript	c.12891G>A	p.Ala4297Ala	synonymous_variant	85/98	ENST00000683500.2	NP_001278744.1	A0A804HLC3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HMCN2	ENST00000683500.2 linkuse as main transcript	c.12891G>A	p.Ala4297Ala	synonymous_variant	85/98		NM_001291815.2	ENSP00000508292.2	A0A804HLC3
HMCN2	ENST00000624552.4 linkuse as main transcript	c.12834G>A	p.Ala4278Ala	synonymous_variant	85/98	5		ENSP00000485357.2	Q8NDA2
HMCN2	ENST00000487727.6 linkuse as main transcript	n.*2483G>A		non_coding_transcript_exon_variant	28/29	5		ENSP00000485578.1	A0A096LPG1
HMCN2	ENST00000487727.6 linkuse as main transcript	n.*2483G>A		3_prime_UTR_variant	28/29	5		ENSP00000485578.1	A0A096LPG1

Frequencies

GnomAD3 genomes

AF:

0.00419

AC:

637

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00864

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.00642

Gnomad ASJ

AF:

0.0179

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00116

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00308

AC:

459

AN:

149006

Hom.:

AF XY:

0.00282

AC XY:

226

AN XY:

80230

show subpopulations

Gnomad AFR exome

AF:

0.00973

Gnomad AMR exome

AF:

0.00427

Gnomad ASJ exome

AF:

0.0187

Gnomad EAS exome

AF:

0.0000927

Gnomad SAS exome

AF:

0.000399

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00173

Gnomad OTH exome

AF:

0.00603

GnomAD4 exome

AF:

0.00179

AC:

2508

AN:

1398272

Hom.:

Cov.:

AF XY:

0.00176

AC XY:

1213

AN XY:

689654

show subpopulations

Gnomad4 AFR exome

AF:

0.0102

Gnomad4 AMR exome

AF:

0.00454

Gnomad4 ASJ exome

AF:

0.0176

Gnomad4 EAS exome

AF:

0.000168

Gnomad4 SAS exome

AF:

0.000379

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00113

Gnomad4 OTH exome

AF:

0.00436

GnomAD4 genome

AF:

0.00420

AC:

639

AN:

152284

Hom.:

Cov.:

AF XY:

0.00416

AC XY:

310

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00861

Gnomad4 AMR

AF:

0.00641

Gnomad4 ASJ

AF:

0.0179

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00116

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.00354

Hom.:

Bravo

AF:

0.00465

Asia WGS

AF:

0.00346

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

Nov 01, 2022

HMCN2: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.81

DANN

Benign

0.85

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