9-130407868-A-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMCN2	NM_001291815.2	c.12688+163A>G		intron_variant	Intron 83 of 97	ENST00000683500.2	NP_001278744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMCN2	ENST00000683500.2	c.12688+163A>G		intron_variant	Intron 83 of 97		NM_001291815.2	ENSP00000508292.2
HMCN2	ENST00000624552.4	c.12631+163A>G		intron_variant	Intron 83 of 97	5		ENSP00000485357.2
HMCN2	ENST00000487727.6	n.*2280+163A>G		intron_variant	Intron 26 of 28	5		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

Gnomad4 AFR AF: 0.624

Gnomad4 AMR AF: 0.639

Gnomad4 ASJ AF: 0.744

Gnomad4 EAS AF: 0.495

Gnomad4 SAS AF: 0.675

Gnomad4 FIN AF: 0.775

Gnomad4 NFE AF: 0.823

Gnomad4 OTH AF: 0.711

Alfa AF: 0.794 Hom.: 81345

Bravo AF: 0.707

Asia WGS AF: 0.570 AC: 1983 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

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