chr9-130377582-T-C

Position:

• chr9-130377582-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001291815.2(HMCN2):​c.8062-67T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 882,622 control chromosomes in the GnomAD database, including 208,940 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.61 (31205 hom., cov: 33)
  • Exomes 𝑓: 0.69 (177735 hom.)
• Consequence: HMCN2 NM_001291815.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMCN2	NM_001291815.2	c.8062-67T>C		intron_variant		ENST00000683500.2	NP_001278744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMCN2	ENST00000683500.2	c.8062-67T>C		intron_variant			NM_001291815.2	ENSP00000508292.2
HMCN2	ENST00000624552.4	c.8062-67T>C		intron_variant		5		ENSP00000485357.2

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92821 AN: 152032 Hom.: 31204 Cov.: 33

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.725

Gnomad ASJ AF: 0.658

Gnomad EAS AF: 0.865

Gnomad SAS AF: 0.699

Gnomad FIN AF: 0.805

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.712

Gnomad OTH AF: 0.636

GnomAD4 exome AF: 0.695 AC: 507599 AN: 730472 Hom.: 177735 AF XY: 0.695 AC XY: 236083 AN XY: 339772

Gnomad4 AFR exome AF: 0.258

Gnomad4 AMR exome AF: 0.768

Gnomad4 ASJ exome AF: 0.631

Gnomad4 EAS exome AF: 0.873

Gnomad4 SAS exome AF: 0.696

Gnomad4 FIN exome AF: 0.800

Gnomad4 NFE exome AF: 0.704

Gnomad4 OTH exome AF: 0.683

GnomAD4 genome AF: 0.610 AC: 92820 AN: 152150 Hom.: 31205 Cov.: 33 AF XY: 0.618 AC XY: 45999 AN XY: 74406

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.725

Gnomad4 ASJ AF: 0.658

Gnomad4 EAS AF: 0.865

Gnomad4 SAS AF: 0.698

Gnomad4 FIN AF: 0.805

Gnomad4 NFE AF: 0.712

Gnomad4 OTH AF: 0.638

Alfa AF: 0.689 Hom.: 46826

Bravo AF: 0.588

Asia WGS AF: 0.770 AC: 2673 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.0
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7020021; hg19: chr9-133252969;