Variant chr9-130354932-C-T 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.5034C>T(p.Asp1678Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00335 in 1,303,718 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0035 ( 16 hom. )

Consequence

HMCN2
NM_001291815.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.51

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 9-130354932-C-T is Benign according to our data. Variant chr9-130354932-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2659590.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-4.51 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMCN2	NM_001291815.2 linkuse as main transcript	c.5034C>T	p.Asp1678Asp	synonymous_variant	32/98	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.5034C>T	p.Asp1678Asp	synonymous_variant	32/98		NM_001291815.2	ENSP00000508292.2		A0A804HLC3
HMCN2	ENST00000624552.4 linkuse as main transcript	c.5034C>T	p.Asp1678Asp	synonymous_variant	32/98	5		ENSP00000485357.2		Q8NDA2

Frequencies

GnomAD3 genomes

AF:

0.00260

AC:

396

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00217

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00376

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00235

AC:

345

AN:

146594

Hom.:

AF XY:

0.00243

AC XY:

192

AN XY:

79074

show subpopulations

Gnomad AFR exome

AF:

0.00150

Gnomad AMR exome

AF:

0.00114

Gnomad ASJ exome

AF:

0.000119

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00338

Gnomad FIN exome

AF:

0.0000659

Gnomad NFE exome

AF:

0.00405

Gnomad OTH exome

AF:

0.00211

GnomAD4 exome

AF:

0.00345

AC:

3977

AN:

1151428

Hom.:

Cov.:

AF XY:

0.00344

AC XY:

1943

AN XY:

564592

show subpopulations

Gnomad4 AFR exome

AF:

0.00192

Gnomad4 AMR exome

AF:

0.00134

Gnomad4 ASJ exome

AF:

0.000188

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00287

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.00387

Gnomad4 OTH exome

AF:

0.00228

GnomAD4 genome

AF:

0.00260

AC:

396

AN:

152290

Hom.:

Cov.:

AF XY:

0.00235

AC XY:

175

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00216

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00393

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00376

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00275

Hom.:

Bravo

AF:

0.00279

Asia WGS

AF:

0.000866

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

0.096

DANN

Benign

0.43

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