rs553024377

Variant names:

• chr9-130353063-C-G
• rs553024377
• NM_001291815.2:c.4722C>G

Your query was ambiguous. Multiple possible variants found:

• chr9-130353063-C-G
• chr9-130353063-C-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.4722C>G​(p.Pro1574Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000445 in 1,304,208 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00025 (2 hom.)
• Consequence: HMCN2 NM_001291815.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.404
• 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 (REVEL=0.012).
• BP6: Variant 9-130353063-C-G is Benign according to our data. Variant chr9-130353063-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2659587.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.404 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 2 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.4722C>G	p.Pro1574Pro	synonymous	Exon 31 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.4722C>G	p.Pro1574Pro	synonymous	Exon 31 of 98	ENSP00000508292.2	Q8NDA2-5
	HMCN2	ENST00000624552.4	TSL:5	c.4722C>G	p.Pro1574Pro	synonymous	Exon 31 of 98	ENSP00000485357.2	Q8NDA2-1

Frequencies

GnomAD3 genomes AF: 0.00194 AC: 295 AN: 152192 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00671

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000580 AC: 85 AN: 146578 AF XY: 0.000418

Gnomad AFR exome AF: 0.00962

Gnomad AMR exome AF: 0.000693

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000185

Gnomad OTH exome AF: 0.000235

GnomAD4 exome AF: 0.000248 AC: 286 AN: 1151898 Hom.: 2 Cov.: 31 AF XY: 0.000205 AC XY: 116 AN XY: 564820

African (AFR) AF: 0.00872 AC: 213 AN: 24418

American (AMR) AF: 0.000602 AC: 17 AN: 28250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15940

East Asian (EAS) AF: 0.00 AC: 0 AN: 12844

South Asian (SAS) AF: 0.00 AC: 0 AN: 76190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27332

Middle Eastern (MID) AF: 0.000454 AC: 2 AN: 4404

European-Non Finnish (NFE) AF: 0.0000304 AC: 28 AN: 920904

Other (OTH) AF: 0.000625 AC: 26 AN: 41616

GnomAD4 genome AF: 0.00194 AC: 295 AN: 152310 Hom.: 1 Cov.: 33 AF XY: 0.00195 AC XY: 145 AN XY: 74468

African (AFR) AF: 0.00669 AC: 278 AN: 41562

American (AMR) AF: 0.000784 AC: 12 AN: 15310

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68030

Other (OTH) AF: 0.000474 AC: 1 AN: 2108

Alfa AF: 0.000201 Hom.: 0

Bravo AF: 0.00244

Asia WGS AF: 0.000289 AC: 1 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	-0.83
CADD	Benign	0.97
DANN	Benign	0.52
PhyloP100		-0.40

Splicing

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

Other links and lift over

dbSNP: rs553024377; hg19: chr9-133228450;