Variant chr9-130418919-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.13109G>A(p.Arg4370Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00339 in 1,548,144 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 7/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0029 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0034 ( 13 hom. )

Consequence

HMCN2
NM_001291815.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.13

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 (MetaRNN=0.0041008294).

BP6

Variant 9-130418919-G-A is Benign according to our data. Variant chr9-130418919-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2659602.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMCN2	NM_001291815.2 linkuse as main transcript	c.13109G>A	p.Arg4370Gln	missense_variant	86/98	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.13109G>A	p.Arg4370Gln	missense_variant	86/98		NM_001291815.2	ENSP00000508292.2	A0A804HLC3
HMCN2	ENST00000624552.4 linkuse as main transcript	c.13052G>A	p.Arg4351Gln	missense_variant	86/98	5		ENSP00000485357.2	Q8NDA2
HMCN2	ENST00000487727.6 linkuse as main transcript	n.*2701G>A		non_coding_transcript_exon_variant	29/29	5		ENSP00000485578.1	A0A096LPG1
HMCN2	ENST00000487727.6 linkuse as main transcript	n.*2701G>A		3_prime_UTR_variant	29/29	5		ENSP00000485578.1	A0A096LPG1

Frequencies

GnomAD3 genomes

AF:

0.00291

AC:

443

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00150

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00602

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00469

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00277

AC:

403

AN:

145358

Hom.:

AF XY:

0.00273

AC XY:

214

AN XY:

78420

show subpopulations

Gnomad AFR exome

AF:

0.000593

Gnomad AMR exome

AF:

0.00214

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000188

Gnomad SAS exome

AF:

0.000808

Gnomad FIN exome

AF:

0.00751

Gnomad NFE exome

AF:

0.00372

Gnomad OTH exome

AF:

0.00285

GnomAD4 exome

AF:

0.00345

AC:

4812

AN:

1395804

Hom.:

Cov.:

AF XY:

0.00338

AC XY:

2323

AN XY:

688222

show subpopulations

Gnomad4 AFR exome

AF:

0.000571

Gnomad4 AMR exome

AF:

0.00198

Gnomad4 ASJ exome

AF:

0.0000798

Gnomad4 EAS exome

AF:

0.0000840

Gnomad4 SAS exome

AF:

0.000810

Gnomad4 FIN exome

AF:

0.00772

Gnomad4 NFE exome

AF:

0.00381

Gnomad4 OTH exome

AF:

0.00295

GnomAD4 genome

AF:

0.00291

AC:

443

AN:

152340

Hom.:

Cov.:

AF XY:

0.00299

AC XY:

223

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000553

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.00602

Gnomad4 NFE

AF:

0.00469

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00339

Hom.:

Bravo

AF:

0.00252

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00234

AC:

ExAC

AF:

0.00167

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

Jan 01, 2023

HMCN2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0015

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.61

MetaRNN

Benign

0.0041

MetaSVM

Benign

-0.98

Sift4G

Uncertain

0.040

Vest4

0.045

MVP

0.048

ClinPred

0.0014

GERP RS

-0.90

Varity_R

0.039

gMVP

0.15

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