chr9-130348669-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001291815.2(HMCN2):​c.4149G>A​(p.Ala1383Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0019 in 1,225,108 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0023 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0018 (7 hom.)
• Consequence: HMCN2 NM_001291815.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.038).
• BP6: Variant 9-130348669-G-A is Benign according to our data. Variant chr9-130348669-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2659585.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 7 AR gene

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>A	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>A	p.Ala1383Ala	synonymous	Exon 27 of 98	ENSP00000508292.2	Q8NDA2-5
	HMCN2	ENST00000624552.4	TSL:5	c.4149G>A	p.Ala1383Ala	synonymous	Exon 27 of 98	ENSP00000485357.2	Q8NDA2-1

Frequencies

GnomAD3 genomes AF: 0.00232 AC: 346 AN: 148908 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000293

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000199

Gnomad ASJ AF: 0.000583

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000440

Gnomad FIN AF: 0.00402

Gnomad MID AF: 0.00323

Gnomad NFE AF: 0.00424

Gnomad OTH AF: 0.000970

GnomAD2 exomes AF: 0.00149 AC: 218 AN: 146776 AF XY: 0.00128

Gnomad AFR exome AF: 0.000148

Gnomad AMR exome AF: 0.000163

Gnomad ASJ exome AF: 0.000717

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00216

Gnomad NFE exome AF: 0.00308

Gnomad OTH exome AF: 0.00117

GnomAD4 exome AF: 0.00184 AC: 1983 AN: 1076078 Hom.: 7 Cov.: 33 AF XY: 0.00184 AC XY: 976 AN XY: 530614

African (AFR) AF: 0.000131 AC: 3 AN: 22928

American (AMR) AF: 0.000142 AC: 4 AN: 28174

Ashkenazi Jewish (ASJ) AF: 0.000648 AC: 10 AN: 15434

East Asian (EAS) AF: 0.00 AC: 0 AN: 12478

South Asian (SAS) AF: 0.0000938 AC: 7 AN: 74666

European-Finnish (FIN) AF: 0.00300 AC: 82 AN: 27310

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4286

European-Non Finnish (NFE) AF: 0.00214 AC: 1820 AN: 851666

Other (OTH) AF: 0.00146 AC: 57 AN: 39136

GnomAD4 genome AF: 0.00232 AC: 346 AN: 149030 Hom.: 1 Cov.: 33 AF XY: 0.00214 AC XY: 156 AN XY: 72814

African (AFR) AF: 0.000292 AC: 12 AN: 41092

American (AMR) AF: 0.000199 AC: 3 AN: 15078

Ashkenazi Jewish (ASJ) AF: 0.000583 AC: 2 AN: 3428

East Asian (EAS) AF: 0.00 AC: 0 AN: 4806

South Asian (SAS) AF: 0.000440 AC: 2 AN: 4548

European-Finnish (FIN) AF: 0.00402 AC: 39 AN: 9692

Middle Eastern (MID) AF: 0.00347 AC: 1 AN: 288

European-Non Finnish (NFE) AF: 0.00425 AC: 285 AN: 67134

Other (OTH) AF: 0.000960 AC: 2 AN: 2084

Alfa AF: 0.00277 Hom.: 1

Bravo AF: 0.00155

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Benign	0.88
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;