Variant chr9-130348669-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001291815.2(HMCN2):c.4149G>A(p.Ala1383Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0019 in 1,225,108 control chromosomes in the GnomAD database, including 8 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 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0018 ( 7 hom. )

Consequence

HMCN2
NM_001291815.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.422

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 9-130348669-G-A is Benign according to our data. Variant chr9-130348669-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2659585.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMCN2	NM_001291815.2 linkuse as main transcript	c.4149G>A	p.Ala1383Ala	synonymous_variant	27/98	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.4149G>A	p.Ala1383Ala	synonymous_variant	27/98		NM_001291815.2	ENSP00000508292.2		A0A804HLC3
HMCN2	ENST00000624552.4 linkuse as main transcript	c.4149G>A	p.Ala1383Ala	synonymous_variant	27/98	5		ENSP00000485357.2		Q8NDA2

Frequencies

GnomAD3 genomes

AF:

0.00232

AC:

346

AN:

148908

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000293

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000199

Gnomad ASJ

AF:

0.000583

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000440

Gnomad FIN

AF:

0.00402

Gnomad MID

AF:

0.00323

Gnomad NFE

AF:

0.00424

Gnomad OTH

AF:

0.000970

GnomAD3 exomes

AF:

0.00149

AC:

218

AN:

146776

Hom.:

AF XY:

0.00128

AC XY:

101

AN XY:

79142

show subpopulations

Gnomad AFR exome

AF:

0.000148

Gnomad AMR exome

AF:

0.000163

Gnomad ASJ exome

AF:

0.000717

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000888

Gnomad FIN exome

AF:

0.00216

Gnomad NFE exome

AF:

0.00308

Gnomad OTH exome

AF:

0.00117

GnomAD4 exome

AF:

0.00184

AC:

1983

AN:

1076078

Hom.:

Cov.:

AF XY:

0.00184

AC XY:

976

AN XY:

530614

show subpopulations

Gnomad4 AFR exome

AF:

0.000131

Gnomad4 AMR exome

AF:

0.000142

Gnomad4 ASJ exome

AF:

0.000648

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000938

Gnomad4 FIN exome

AF:

0.00300

Gnomad4 NFE exome

AF:

0.00214

Gnomad4 OTH exome

AF:

0.00146

GnomAD4 genome

AF:

0.00232

AC:

346

AN:

149030

Hom.:

Cov.:

AF XY:

0.00214

AC XY:

156

AN XY:

72814

show subpopulations

Gnomad4 AFR

AF:

0.000292

Gnomad4 AMR

AF:

0.000199

Gnomad4 ASJ

AF:

0.000583

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000440

Gnomad4 FIN

AF:

0.00402

Gnomad4 NFE

AF:

0.00425

Gnomad4 OTH

AF:

0.000960

Alfa

AF:

0.00277

Hom.:

Bravo

AF:

0.00155

Asia WGS

AF:

0.000577

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

Jan 01, 2023

HMCN2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.88

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