NM_001291815.2:c.8062-67T>C

Variant names:

• chr9-130377582-T-C
• rs7020021
• NM_001291815.2:c.8062-67T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001291815.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMCN2	NM_001291815.2	MANE Select	c.8062-67T>C		intron	N/A	NP_001278744.1	Q8NDA2-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMCN2	ENST00000683500.2	MANE Select	c.8062-67T>C		intron	N/A	ENSP00000508292.2	Q8NDA2-5
	HMCN2	ENST00000624552.4	TSL:5	c.8062-67T>C		intron	N/A	ENSP00000485357.2	Q8NDA2-1

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

African (AFR) AF: 0.258 AC: 3563 AN: 13828

American (AMR) AF: 0.768 AC: 631 AN: 822

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2841 AN: 4504

East Asian (EAS) AF: 0.873 AC: 2756 AN: 3156

South Asian (SAS) AF: 0.696 AC: 10038 AN: 14426

European-Finnish (FIN) AF: 0.800 AC: 520 AN: 650

Middle Eastern (MID) AF: 0.620 AC: 892 AN: 1438

European-Non Finnish (NFE) AF: 0.704 AC: 469988 AN: 667684

Other (OTH) AF: 0.683 AC: 16370 AN: 23964

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

African (AFR) AF: 0.303 AC: 12569 AN: 41470

American (AMR) AF: 0.725 AC: 11086 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.658 AC: 2283 AN: 3468

East Asian (EAS) AF: 0.865 AC: 4478 AN: 5176

South Asian (SAS) AF: 0.698 AC: 3369 AN: 4824

European-Finnish (FIN) AF: 0.805 AC: 8534 AN: 10598

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.712 AC: 48426 AN: 68004

Other (OTH) AF: 0.638 AC: 1348 AN: 2114

Alfa AF: 0.677 Hom.: 64105

Bravo AF: 0.588

Asia WGS AF: 0.770 AC: 2673 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.0
DANN	Benign	0.55
PhyloP100		0.13

Splicing

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

Other links and lift over

dbSNP: rs7020021; hg19: chr9-133252969;