chr9-130292500-T-C

Position:

• chr9-130292500-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.613-2355T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 152,160 control chromosomes in the GnomAD database, including 11,709 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 0.37 (11709 hom., cov: 33)
• Consequence: HMCN2 NM_001291815.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMCN2	NM_001291815.2	c.613-2355T>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.613-2355T>C		intron_variant			NM_001291815.2	ENSP00000508292.2
HMCN2	ENST00000624552.4	c.613-2355T>C		intron_variant		5		ENSP00000485357.2

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56159 AN: 152042 Hom.: 11695 Cov.: 33

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.382

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.369 AC: 56199 AN: 152160 Hom.: 11709 Cov.: 33 AF XY: 0.370 AC XY: 27513 AN XY: 74376

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.479

Gnomad4 EAS AF: 0.601

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.454

Gnomad4 OTH AF: 0.389

Alfa AF: 0.433 Hom.: 10259

Bravo AF: 0.359

Asia WGS AF: 0.472 AC: 1638 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.2
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4837492; hg19: chr9-133054779;