chr9-130410582-G-C

Variant names:

• chr9-130410582-G-C
• NM_001291815.2:c.12891G>C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001291815.2(HMCN2):​c.12891G>C​(p.Ala4297Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,282 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: HMCN2 NM_001291815.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.25

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP7: Synonymous conserved (PhyloP=-3.25 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMCN2	NM_001291815.2	c.12891G>C	p.Ala4297Ala	synonymous_variant	Exon 85 of 98	ENST00000683500.2	NP_001278744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMCN2	ENST00000683500.2	c.12891G>C	p.Ala4297Ala	synonymous_variant	Exon 85 of 98		NM_001291815.2	ENSP00000508292.2
HMCN2	ENST00000624552.4	c.12834G>C	p.Ala4278Ala	synonymous_variant	Exon 85 of 98	5		ENSP00000485357.2
HMCN2	ENST00000487727.6	n.*2483G>C		non_coding_transcript_exon_variant	Exon 28 of 29	5		ENSP00000485578.1
HMCN2	ENST00000487727.6	n.*2483G>C		3_prime_UTR_variant	Exon 28 of 29	5		ENSP00000485578.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398282 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 689654

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000172

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.14
DANN	Benign	0.75

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-133285969;