chr9-130306895-T-C

Variant names:

• chr9-130306895-T-C
• rs200362767
• NM_001291815.2:c.2043T>C

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.2043T>C​(p.Asn681Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00273 in 471,036 control chromosomes in the GnomAD database, including 12 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 (4 hom., cov: 31)
  • Exomes 𝑓: 0.0030 (8 hom.)
• Consequence: HMCN2 NM_001291815.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.625
• 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 9-130306895-T-C is Benign according to our data. Variant chr9-130306895-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2659583.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.625 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 4 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.2043T>C	p.Asn681Asn	synonymous	Exon 13 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.2043T>C	p.Asn681Asn	synonymous	Exon 13 of 98	ENSP00000508292.2	Q8NDA2-5
	HMCN2	ENST00000624552.4	TSL:5	c.2043T>C	p.Asn681Asn	synonymous	Exon 13 of 98	ENSP00000485357.2	Q8NDA2-1

Frequencies

GnomAD3 genomes AF: 0.00226 AC: 344 AN: 152056 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.000917

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00395

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00400

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00249 AC: 373 AN: 149882 AF XY: 0.00269

Gnomad AFR exome AF: 0.000730

Gnomad AMR exome AF: 0.000489

Gnomad ASJ exome AF: 0.000358

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00166

Gnomad NFE exome AF: 0.00427

Gnomad OTH exome AF: 0.00299

GnomAD4 exome AF: 0.00295 AC: 942 AN: 318862 Hom.: 8 Cov.: 0 AF XY: 0.00304 AC XY: 548 AN XY: 180122

African (AFR) AF: 0.000811 AC: 7 AN: 8632

American (AMR) AF: 0.000586 AC: 16 AN: 27282

Ashkenazi Jewish (ASJ) AF: 0.000278 AC: 3 AN: 10788

East Asian (EAS) AF: 0.00 AC: 0 AN: 9210

South Asian (SAS) AF: 0.00293 AC: 175 AN: 59728

European-Finnish (FIN) AF: 0.00155 AC: 42 AN: 27068

Middle Eastern (MID) AF: 0.00108 AC: 3 AN: 2766

European-Non Finnish (NFE) AF: 0.00420 AC: 668 AN: 159020

Other (OTH) AF: 0.00195 AC: 28 AN: 14368

GnomAD4 genome AF: 0.00226 AC: 344 AN: 152174 Hom.: 4 Cov.: 31 AF XY: 0.00219 AC XY: 163 AN XY: 74418

African (AFR) AF: 0.000506 AC: 21 AN: 41504

American (AMR) AF: 0.000916 AC: 14 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00396 AC: 19 AN: 4804

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10612

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

European-Non Finnish (NFE) AF: 0.00400 AC: 272 AN: 68006

Other (OTH) AF: 0.00284 AC: 6 AN: 2110

Alfa AF: 0.00376 Hom.: 0

Bravo AF: 0.00232

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

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	-0.87
CADD	Benign	2.4
DANN	Benign	0.40
PhyloP100		-0.63

Splicing

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

Other links and lift over

dbSNP: rs200362767; hg19: chr9-133069174;