Variant chr9-130384761-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_001291815.2(HMCN2):c.9069C>T(p.Ala3023Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00604 in 1,303,284 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0057 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0061 ( 30 hom. )

Consequence

HMCN2
NM_001291815.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.23

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.27).

BP6

Variant 9-130384761-C-T is Benign according to our data. Variant chr9-130384761-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2659595.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.23 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.9069C>T	p.Ala3023Ala	synonymous_variant	59/98	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.9069C>T	p.Ala3023Ala	synonymous_variant	59/98		NM_001291815.2	ENSP00000508292.2	A0A804HLC3
HMCN2	ENST00000624552.4 linkuse as main transcript	c.9069C>T	p.Ala3023Ala	synonymous_variant	59/98	5		ENSP00000485357.2	Q8NDA2
HMCN2	ENST00000487727.6 linkuse as main transcript	n.162C>T		non_coding_transcript_exon_variant	2/29	5		ENSP00000485578.1	A0A096LPG1

Frequencies

GnomAD3 genomes

AF:

0.00569

AC:

866

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00648

Gnomad ASJ

AF:

0.00837

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00870

Gnomad FIN

AF:

0.0175

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00663

Gnomad OTH

AF:

0.00480

GnomAD3 exomes

AF:

0.00612

AC:

906

AN:

148122

Hom.:

AF XY:

0.00653

AC XY:

522

AN XY:

79884

show subpopulations

Gnomad AFR exome

AF:

0.00103

Gnomad AMR exome

AF:

0.00391

Gnomad ASJ exome

AF:

0.00848

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00546

Gnomad FIN exome

AF:

0.0149

Gnomad NFE exome

AF:

0.00616

Gnomad OTH exome

AF:

0.00768

GnomAD4 exome

AF:

0.00608

AC:

7002

AN:

1151018

Hom.:

Cov.:

AF XY:

0.00623

AC XY:

3518

AN XY:

564458

show subpopulations

Gnomad4 AFR exome

AF:

0.000983

Gnomad4 AMR exome

AF:

0.00361

Gnomad4 ASJ exome

AF:

0.00916

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00604

Gnomad4 FIN exome

AF:

0.0148

Gnomad4 NFE exome

AF:

0.00610

Gnomad4 OTH exome

AF:

0.00574

GnomAD4 genome

AF:

0.00569

AC:

867

AN:

152266

Hom.:

Cov.:

AF XY:

0.00663

AC XY:

494

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.00660

Gnomad4 ASJ

AF:

0.00837

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00871

Gnomad4 FIN

AF:

0.0175

Gnomad4 NFE

AF:

0.00662

Gnomad4 OTH

AF:

0.00475

Alfa

AF:

0.00561

Hom.:

Bravo

AF:

0.00473

Asia WGS

AF:

0.00231

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

May 01, 2022

HMCN2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.27

CADD

Benign

4.1

DANN

Benign

0.64

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