9-130348669-G-C

Variant names:

• chr9-130348669-G-C
• rs200403870
• NM_001291815.2:c.4149G>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001291815.2(HMCN2):​c.4149G>C​(p.Ala1383Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A1383A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: HMCN2 NM_001291815.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.422
• Publications: 1 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.02).
• BP7: Synonymous conserved (PhyloP=0.422 with no splicing effect.

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.4149G>C	p.Ala1383Ala	synonymous	Exon 27 of 98	NP_001278744.1	Q8NDA2-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMCN2	ENST00000683500.2	MANE Select	c.4149G>C	p.Ala1383Ala	synonymous	Exon 27 of 98	ENSP00000508292.2	Q8NDA2-5
	HMCN2	ENST00000624552.4	TSL:5	c.4149G>C	p.Ala1383Ala	synonymous	Exon 27 of 98	ENSP00000485357.2	Q8NDA2-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	7.5
DANN	Benign	0.77
PhyloP100		0.42

Splicing

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

Other links and lift over

dbSNP: rs200403870; hg19: chr9-133224056;