Variant 9-130391304-G-A 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.9768G>A(p.Pro3256Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000587 in 987,672 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 4 hom., cov: 33)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

HMCN2
NM_001291815.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.51

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=-0.9).

BP6

Variant 9-130391304-G-A is Benign according to our data. Variant chr9-130391304-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2659596.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-4.51 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMCN2	NM_001291815.2 linkuse as main transcript	c.9768G>A	p.Pro3256Pro	synonymous_variant	64/98	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.9768G>A	p.Pro3256Pro	synonymous_variant	64/98		NM_001291815.2	ENSP00000508292.2	A0A804HLC3
HMCN2	ENST00000624552.4 linkuse as main transcript	c.9768G>A	p.Pro3256Pro	synonymous_variant	64/98	5		ENSP00000485357.2	Q8NDA2
HMCN2	ENST00000487727.6 linkuse as main transcript	n.861G>A		non_coding_transcript_exon_variant	7/29	5		ENSP00000485578.1	A0A096LPG1

Frequencies

GnomAD3 genomes

AF:

0.00271

AC:

412

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00890

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00222

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.000956

GnomAD4 exome

AF:

0.000200

AC:

167

AN:

835340

Hom.:

Cov.:

AF XY:

0.000158

AC XY:

AN XY:

385834

show subpopulations

Gnomad4 AFR exome

AF:

0.00769

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000394

Gnomad4 OTH exome

AF:

0.000400

GnomAD4 genome

AF:

0.00271

AC:

413

AN:

152332

Hom.:

Cov.:

AF XY:

0.00258

AC XY:

192

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00890

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000278

Hom.:

Bravo

AF:

0.00337

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

-0.90

CADD

Benign

0.40

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