Variant 9-130306895-T-C 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.2043T>C(p.Asn681Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00273 in 471,036 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 4 hom., cov: 31)

Exomes 𝑓: 0.0030 ( 8 hom. )

Consequence

HMCN2
NM_001291815.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.625

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=-0.87).

BP6

Variant 9-130306895-T-C is Benign according to our data. Variant chr9-130306895-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2659583.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.625 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMCN2	NM_001291815.2 linkuse as main transcript	c.2043T>C	p.Asn681Asn	synonymous_variant	13/98	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.2043T>C	p.Asn681Asn	synonymous_variant	13/98		NM_001291815.2	ENSP00000508292.2		A0A804HLC3
HMCN2	ENST00000624552.4 linkuse as main transcript	c.2043T>C	p.Asn681Asn	synonymous_variant	13/98	5		ENSP00000485357.2		Q8NDA2

Frequencies

GnomAD3 genomes

AF:

0.00226

AC:

344

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.000917

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00395

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00400

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00249

AC:

373

AN:

149882

Hom.:

AF XY:

0.00269

AC XY:

217

AN XY:

80566

show subpopulations

Gnomad AFR exome

AF:

0.000730

Gnomad AMR exome

AF:

0.000489

Gnomad ASJ exome

AF:

0.000358

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00333

Gnomad FIN exome

AF:

0.00166

Gnomad NFE exome

AF:

0.00427

Gnomad OTH exome

AF:

0.00299

GnomAD4 exome

AF:

0.00295

AC:

942

AN:

318862

Hom.:

Cov.:

AF XY:

0.00304

AC XY:

548

AN XY:

180122

show subpopulations

Gnomad4 AFR exome

AF:

0.000811

Gnomad4 AMR exome

AF:

0.000586

Gnomad4 ASJ exome

AF:

0.000278

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00293

Gnomad4 FIN exome

AF:

0.00155

Gnomad4 NFE exome

AF:

0.00420

Gnomad4 OTH exome

AF:

0.00195

GnomAD4 genome

AF:

0.00226

AC:

344

AN:

152174

Hom.:

Cov.:

AF XY:

0.00219

AC XY:

163

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.000506

Gnomad4 AMR

AF:

0.000916

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00396

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00400

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00376

Hom.:

Bravo

AF:

0.00232

Asia WGS

AF:

0.00144

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

Sep 01, 2022

HMCN2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.4

DANN

Benign

0.40

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