Variant 9-130395332-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.10896C>T(p.Asp3632Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00848 in 1,288,534 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0066 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0087 ( 46 hom. )

Consequence

HMCN2
NM_001291815.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.47

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=-0.8).

BP6

Variant 9-130395332-C-T is Benign according to our data. Variant chr9-130395332-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2659597.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.47 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMCN2	NM_001291815.2 linkuse as main transcript	c.10896C>T	p.Asp3632Asp	synonymous_variant	71/98	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.10896C>T	p.Asp3632Asp	synonymous_variant	71/98		NM_001291815.2	ENSP00000508292.2	A0A804HLC3
HMCN2	ENST00000624552.4 linkuse as main transcript	c.10896C>T	p.Asp3632Asp	synonymous_variant	71/98	5		ENSP00000485357.2	Q8NDA2
HMCN2	ENST00000487727.6 linkuse as main transcript	n.*545C>T		non_coding_transcript_exon_variant	14/29	5		ENSP00000485578.1	A0A096LPG1
HMCN2	ENST00000487727.6 linkuse as main transcript	n.*545C>T		3_prime_UTR_variant	14/29	5		ENSP00000485578.1	A0A096LPG1

Frequencies

GnomAD3 genomes

AF:

0.00664

AC:

1010

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00164

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00818

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.0137

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00960

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00577

AC:

768

AN:

133044

Hom.:

AF XY:

0.00547

AC XY:

396

AN XY:

72422

show subpopulations

Gnomad AFR exome

AF:

0.00140

Gnomad AMR exome

AF:

0.00495

Gnomad ASJ exome

AF:

0.000490

Gnomad EAS exome

AF:

0.000191

Gnomad SAS exome

AF:

0.000986

Gnomad FIN exome

AF:

0.0130

Gnomad NFE exome

AF:

0.00985

Gnomad OTH exome

AF:

0.00733

GnomAD4 exome

AF:

0.00873

AC:

9919

AN:

1136288

Hom.:

Cov.:

AF XY:

0.00839

AC XY:

4674

AN XY:

557410

show subpopulations

Gnomad4 AFR exome

AF:

0.00135

Gnomad4 AMR exome

AF:

0.00488

Gnomad4 ASJ exome

AF:

0.000253

Gnomad4 EAS exome

AF:

0.000156

Gnomad4 SAS exome

AF:

0.000789

Gnomad4 FIN exome

AF:

0.0130

Gnomad4 NFE exome

AF:

0.0100

Gnomad4 OTH exome

AF:

0.00636

GnomAD4 genome

AF:

0.00663

AC:

1009

AN:

152246

Hom.:

Cov.:

AF XY:

0.00685

AC XY:

510

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00164

Gnomad4 AMR

AF:

0.00817

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.0137

Gnomad4 NFE

AF:

0.00959

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00614

Hom.:

Bravo

AF:

0.00628

Asia WGS

AF:

0.00144

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

Oct 01, 2022

HMCN2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.049

DANN

Benign

0.73

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