9-130395332-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001291815.2(HMCN2):​c.10896C>T​(p.Asp3632Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00848 in 1,288,534 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0066 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0087 (46 hom.)
• Consequence: HMCN2 NM_001291815.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 9-130395332-C-T is Benign according to our data. Variant chr9-130395332-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2659597.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.47 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 8 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.10896C>T	p.Asp3632Asp	synonymous	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>T	p.Asp3632Asp	synonymous	Exon 71 of 98	ENSP00000508292.2	Q8NDA2-5
	HMCN2	ENST00000624552.4	TSL:5	c.10896C>T	p.Asp3632Asp	synonymous	Exon 71 of 98	ENSP00000485357.2	Q8NDA2-1
	HMCN2	ENST00000487727.6	TSL:5	n.*545C>T		non_coding_transcript_exon	Exon 14 of 29	ENSP00000485578.1	A0A096LPG1

Frequencies

GnomAD3 genomes AF: 0.00664 AC: 1010 AN: 152128 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00164

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00818

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.0137

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00960

Gnomad OTH AF: 0.00669

GnomAD2 exomes AF: 0.00577 AC: 768 AN: 133044 AF XY: 0.00547

Gnomad AFR exome AF: 0.00140

Gnomad AMR exome AF: 0.00495

Gnomad ASJ exome AF: 0.000490

Gnomad EAS exome AF: 0.000191

Gnomad FIN exome AF: 0.0130

Gnomad NFE exome AF: 0.00985

Gnomad OTH exome AF: 0.00733

GnomAD4 exome AF: 0.00873 AC: 9919 AN: 1136288 Hom.: 46 Cov.: 32 AF XY: 0.00839 AC XY: 4674 AN XY: 557410

African (AFR) AF: 0.00135 AC: 33 AN: 24378

American (AMR) AF: 0.00488 AC: 137 AN: 28052

Ashkenazi Jewish (ASJ) AF: 0.000253 AC: 4 AN: 15816

East Asian (EAS) AF: 0.000156 AC: 2 AN: 12840

South Asian (SAS) AF: 0.000789 AC: 60 AN: 76040

European-Finnish (FIN) AF: 0.0130 AC: 169 AN: 13020

Middle Eastern (MID) AF: 0.000913 AC: 4 AN: 4382

European-Non Finnish (NFE) AF: 0.0100 AC: 9246 AN: 920272

Other (OTH) AF: 0.00636 AC: 264 AN: 41488

GnomAD4 genome AF: 0.00663 AC: 1009 AN: 152246 Hom.: 8 Cov.: 32 AF XY: 0.00685 AC XY: 510 AN XY: 74438

African (AFR) AF: 0.00164 AC: 68 AN: 41558

American (AMR) AF: 0.00817 AC: 125 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5166

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4816

European-Finnish (FIN) AF: 0.0137 AC: 145 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00959 AC: 652 AN: 67994

Other (OTH) AF: 0.00662 AC: 14 AN: 2114

Alfa AF: 0.00614 Hom.: 0

Bravo AF: 0.00628

Asia WGS AF: 0.00144 AC: 5 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	-0.80
CADD	Benign	0.049
DANN	Benign	0.73
PhyloP100		-3.5

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;