9-130286317-A-C

Position:

• chr9-130286317-A-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001291815.2(HMCN2):​c.612+7A>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00875 in 470,826 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0078 (6 hom., cov: 33)
  • Exomes 𝑓: 0.0092 (29 hom.)
• Consequence: HMCN2 NM_001291815.2 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.194

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 9-130286317-A-C is Benign according to our data. Variant chr9-130286317-A-C is described in ClinVar as [Benign]. Clinvar id is 2659580.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMCN2	NM_001291815.2	c.612+7A>C		splice_region_variant, intron_variant		ENST00000683500.2	NP_001278744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMCN2	ENST00000683500.2	c.612+7A>C		splice_region_variant, intron_variant			NM_001291815.2	ENSP00000508292.2
HMCN2	ENST00000624552.4	c.612+7A>C		splice_region_variant, intron_variant		5		ENSP00000485357.2

Frequencies

GnomAD3 genomes AF: 0.00777 AC: 1183 AN: 152184 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.00154

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.00727

Gnomad ASJ AF: 0.0164

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.0235

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00970

Gnomad OTH AF: 0.00716

GnomAD3 exomes AF: 0.00868 AC: 1274 AN: 146704 Hom.: 17 AF XY: 0.00815 AC XY: 645 AN XY: 79110

Gnomad AFR exome AF: 0.000889

Gnomad AMR exome AF: 0.00530

Gnomad ASJ exome AF: 0.0139

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00169

Gnomad FIN exome AF: 0.0265

Gnomad NFE exome AF: 0.00971

Gnomad OTH exome AF: 0.0117

GnomAD4 exome AF: 0.00922 AC: 2937 AN: 318524 Hom.: 29 Cov.: 0 AF XY: 0.00864 AC XY: 1554 AN XY: 179960

Gnomad4 AFR exome AF: 0.00174

Gnomad4 AMR exome AF: 0.00528

Gnomad4 ASJ exome AF: 0.0147

Gnomad4 EAS exome AF: 0.000217

Gnomad4 SAS exome AF: 0.00233

Gnomad4 FIN exome AF: 0.0266

Gnomad4 NFE exome AF: 0.00991

Gnomad4 OTH exome AF: 0.0109

GnomAD4 genome AF: 0.00777 AC: 1184 AN: 152302 Hom.: 6 Cov.: 33 AF XY: 0.00824 AC XY: 614 AN XY: 74478

Gnomad4 AFR AF: 0.00154

Gnomad4 AMR AF: 0.00726

Gnomad4 ASJ AF: 0.0164

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.00332

Gnomad4 FIN AF: 0.0235

Gnomad4 NFE AF: 0.00970

Gnomad4 OTH AF: 0.00756

Alfa AF: 0.00863 Hom.: 6

Bravo AF: 0.00666

Asia WGS AF: 0.00953 AC: 33 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2023

HMCN2: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.67
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs150947458; hg19: chr9-133048596;