NM_001291815.2:c.11772C>A

Variant names:

• chr9-130402790-C-A
• rs748735294
• NM_001291815.2:c.11772C>A

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.11772C>A​(p.Gly3924Gly) variant causes a splice region, 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. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: HMCN2 NM_001291815.2 splice_region, synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.92

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=-0.93).
• BP7: Synonymous conserved (PhyloP=-3.92 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMCN2	NM_001291815.2	c.11772C>A	p.Gly3924Gly	splice_region_variant, synonymous_variant	Exon 78 of 98	ENST00000683500.2	NP_001278744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMCN2	ENST00000683500.2	c.11772C>A	p.Gly3924Gly	splice_region_variant, synonymous_variant	Exon 78 of 98		NM_001291815.2	ENSP00000508292.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.0030
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs748735294; hg19: chr9-133278177;