chr9-130379397-AC-A

Position:

• chr9-130379397-AC-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001291815.2(HMCN2):​c.8366delC​(p.Pro2789fs) variant causes a frameshift change. The variant allele was found at a frequency of 0.000384 in 985,550 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.00057 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00035 (0 hom.)
• Consequence: HMCN2 NM_001291815.2 frameshift
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.71

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 9-130379397-AC-A is Benign according to our data. Variant chr9-130379397-AC-A is described in ClinVar as [Likely_benign]. Clinvar id is 2659594.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMCN2	NM_001291815.2	c.8366delC	p.Pro2789fs	frameshift_variant	54/98	ENST00000683500.2	NP_001278744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMCN2	ENST00000683500.2	c.8366delC	p.Pro2789fs	frameshift_variant	54/98		NM_001291815.2	ENSP00000508292.2
HMCN2	ENST00000624552.4	c.8366delC	p.Pro2789fs	frameshift_variant	54/98	5		ENSP00000485357.2

Frequencies

GnomAD3 genomes AF: 0.000573 AC: 87 AN: 151876 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000442

Gnomad OTH AF: 0.000957

GnomAD4 exome AF: 0.000349 AC: 291 AN: 833556 Hom.: 0 Cov.: 30 AF XY: 0.000353 AC XY: 136 AN XY: 384984

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0101

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000790

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000240

Gnomad4 OTH exome AF: 0.00150

GnomAD4 genome AF: 0.000572 AC: 87 AN: 151994 Hom.: 1 Cov.: 32 AF XY: 0.000565 AC XY: 42 AN XY: 74314

Gnomad4 AFR AF: 0.0000483

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.0121

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000442

Gnomad4 OTH AF: 0.000947

Bravo AF: 0.000518

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2023

HMCN2: BS1 -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1017406376; hg19: chr9-133254784;