chr9-130424860-ACT-A

Position:

• chr9-130424860-ACT-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001291815.2(HMCN2):​c.13471_13472delCT​(p.Leu4491fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000808 in 1,472,280 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely benign (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.00084 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00080 (2 hom.)
• Consequence: HMCN2 NM_001291815.2 frameshift
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.525

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]

LOC107987134 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 9-130424860-ACT-A is Benign according to our data. Variant chr9-130424860-ACT-A is described in ClinVar as [Likely_benign]. Clinvar id is 2659604.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMCN2	NM_001291815.2	c.13471_13472delCT	p.Leu4491fs	frameshift_variant	88/98	ENST00000683500.2	NP_001278744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMCN2	ENST00000683500.2	c.13471_13472delCT	p.Leu4491fs	frameshift_variant	88/98		NM_001291815.2	ENSP00000508292.2
HMCN2	ENST00000624552.4	c.13414_13415delCT	p.Leu4472fs	frameshift_variant	88/98	5		ENSP00000485357.2

Frequencies

GnomAD3 genomes AF: 0.000842 AC: 128 AN: 152050 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00282

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.000915 AC: 84 AN: 91780 Hom.: 0 AF XY: 0.000933 AC XY: 44 AN XY: 47178

Gnomad AFR exome AF: 0.000329

Gnomad AMR exome AF: 0.00104

Gnomad ASJ exome AF: 0.00743

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000613

Gnomad FIN exome AF: 0.0000752

Gnomad NFE exome AF: 0.000925

Gnomad OTH exome AF: 0.00185

GnomAD4 exome AF: 0.000804 AC: 1062 AN: 1320112 Hom.: 2 AF XY: 0.000815 AC XY: 523 AN XY: 641346

Gnomad4 AFR exome AF: 0.000172

Gnomad4 AMR exome AF: 0.00179

Gnomad4 ASJ exome AF: 0.00791

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000238

Gnomad4 FIN exome AF: 0.0000658

Gnomad4 NFE exome AF: 0.000648

Gnomad4 OTH exome AF: 0.00162

GnomAD4 genome AF: 0.000841 AC: 128 AN: 152168 Hom.: 1 Cov.: 31 AF XY: 0.000793 AC XY: 59 AN XY: 74390

Gnomad4 AFR AF: 0.000217

Gnomad4 AMR AF: 0.00281

Gnomad4 ASJ AF: 0.00692

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000632

Gnomad4 OTH AF: 0.00427

Alfa AF: 0.00200 Hom.: 1

Bravo AF: 0.00119

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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

Jul 01, 2023

HMCN2: BS2 -

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: rs760963111; hg19: chr9-133300247;