rs116972695

Variant names:

• chr9-130395332-C-A
• rs116972695
• NM_001291815.2:c.10896C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-130395332-C-A
• chr9-130395332-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001291815.2(HMCN2):​c.10896C>A​(p.Asp3632Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000352 in 1,136,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 7/10 in silico tools predict 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. D3632D) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: HMCN2 NM_001291815.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.47
• Publications: 0 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04203391).

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.10896C>A	p.Asp3632Glu	missense	Exon 71 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.10896C>A	p.Asp3632Glu	missense	Exon 71 of 98	ENSP00000508292.2	Q8NDA2-5
	HMCN2	ENST00000624552.4	TSL:5	c.10896C>A	p.Asp3632Glu	missense	Exon 71 of 98	ENSP00000485357.2	Q8NDA2-1
	HMCN2	ENST00000487727.6	TSL:5	n.*545C>A		non_coding_transcript_exon	Exon 14 of 29	ENSP00000485578.1	A0A096LPG1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000352 AC: 4 AN: 1136292 Hom.: 0 Cov.: 32 AF XY: 0.00000359 AC XY: 2 AN XY: 557410

African (AFR) AF: 0.00 AC: 0 AN: 24378

American (AMR) AF: 0.00 AC: 0 AN: 28052

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15816

East Asian (EAS) AF: 0.00 AC: 0 AN: 12840

South Asian (SAS) AF: 0.00 AC: 0 AN: 76038

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 13020

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4382

European-Non Finnish (NFE) AF: 0.00000435 AC: 4 AN: 920278

Other (OTH) AF: 0.00 AC: 0 AN: 41488

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.0010
DANN	Benign	0.63
DEOGEN2	Benign	0.028	T
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.48	T
MetaRNN	Benign	0.042	T
PhyloP100		-3.5
Sift4G	Benign	0.84	T
Vest4		0.11
MVP		0.092
GERP RS		-9.7
Varity_R		0.052
gMVP		0.25

Splicing

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

Other links and lift over

dbSNP: rs116972695; hg19: chr9-133270719;