9-130407868-A-G

Variant names:

• chr9-130407868-A-G
• rs10736862
• NM_001291815.2:c.12688+163A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001291815.2(HMCN2):​c.12688+163A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 152,114 control chromosomes in the GnomAD database, including 41,053 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 0.73 (41053 hom., cov: 33)
• Consequence: HMCN2 NM_001291815.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.817 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMCN2	NM_001291815.2	MANE Select	c.12688+163A>G		intron	N/A	NP_001278744.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMCN2	ENST00000683500.2	MANE Select	c.12688+163A>G		intron	N/A	ENSP00000508292.2
	HMCN2	ENST00000624552.4	TSL:5	c.12631+163A>G		intron	N/A	ENSP00000485357.2
	HMCN2	ENST00000487727.6	TSL:5	n.*2280+163A>G		intron	N/A	ENSP00000485578.1

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110556 AN: 151998 Hom.: 41048 Cov.: 33

Gnomad AFR AF: 0.625

Gnomad AMI AF: 0.771

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.775

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.823

Gnomad OTH AF: 0.716

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

GnomAD4 genome AF: 0.727 AC: 110592 AN: 152114 Hom.: 41053 Cov.: 33 AF XY: 0.720 AC XY: 53580 AN XY: 74366

African (AFR) AF: 0.624 AC: 25897 AN: 41474

American (AMR) AF: 0.639 AC: 9770 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.744 AC: 2581 AN: 3470

East Asian (EAS) AF: 0.495 AC: 2553 AN: 5160

South Asian (SAS) AF: 0.675 AC: 3257 AN: 4824

European-Finnish (FIN) AF: 0.775 AC: 8207 AN: 10596

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.823 AC: 55941 AN: 68004

Other (OTH) AF: 0.711 AC: 1497 AN: 2106

Alfa AF: 0.785 Hom.: 193709

Bravo AF: 0.707

Asia WGS AF: 0.570 AC: 1983 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.52
DANN	Benign	0.59
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs10736862; hg19: chr9-133283255; COSMIC: COSV52983407; COSMIC: COSV52983407;