Variant chr9-130424807-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.13413C>T(p.Ile4471Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0055 in 1,538,830 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0041 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0057 ( 36 hom. )

Consequence

HMCN2
NM_001291815.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.39

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:

LOC107987134 (HGNC:):

LOC107987134 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=-0.64).

BP6

Variant 9-130424807-C-T is Benign according to our data. Variant chr9-130424807-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2659603.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.39 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.13413C>T	p.Ile4471Ile	synonymous_variant	88/98	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.13413C>T	p.Ile4471Ile	synonymous_variant	88/98		NM_001291815.2	ENSP00000508292.2		A0A804HLC3
HMCN2	ENST00000624552.4 linkuse as main transcript	c.13356C>T	p.Ile4452Ile	synonymous_variant	88/98	5		ENSP00000485357.2		Q8NDA2

Frequencies

GnomAD3 genomes

AF:

0.00406

AC:

618

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000917

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00517

Gnomad FIN

AF:

0.00235

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00658

Gnomad OTH

AF:

0.00765

GnomAD3 exomes

AF:

0.00456

AC:

640

AN:

140434

Hom.:

AF XY:

0.00513

AC XY:

388

AN XY:

75630

show subpopulations

Gnomad AFR exome

AF:

0.000598

Gnomad AMR exome

AF:

0.00251

Gnomad ASJ exome

AF:

0.00586

Gnomad EAS exome

AF:

0.000192

Gnomad SAS exome

AF:

0.00643

Gnomad FIN exome

AF:

0.00203

Gnomad NFE exome

AF:

0.00660

Gnomad OTH exome

AF:

0.00564

GnomAD4 exome

AF:

0.00565

AC:

7839

AN:

1386506

Hom.:

Cov.:

AF XY:

0.00584

AC XY:

3989

AN XY:

682490

show subpopulations

Gnomad4 AFR exome

AF:

0.000800

Gnomad4 AMR exome

AF:

0.00295

Gnomad4 ASJ exome

AF:

0.00664

Gnomad4 EAS exome

AF:

0.0000846

Gnomad4 SAS exome

AF:

0.00635

Gnomad4 FIN exome

AF:

0.00242

Gnomad4 NFE exome

AF:

0.00614

Gnomad4 OTH exome

AF:

0.00553

GnomAD4 genome

AF:

0.00406

AC:

619

AN:

152324

Hom.:

Cov.:

AF XY:

0.00428

AC XY:

319

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000914

Gnomad4 AMR

AF:

0.00301

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00518

Gnomad4 FIN

AF:

0.00235

Gnomad4 NFE

AF:

0.00660

Gnomad4 OTH

AF:

0.00757

Alfa

AF:

0.00659

Hom.:

Bravo

AF:

0.00381

Asia WGS

AF:

0.00202

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, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

1.5

DANN

Benign

0.65

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