chr9-130391304-G-A

Position:

• chr9-130391304-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001291815.2(HMCN2):​c.9768G>A​(p.Pro3256Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000587 in 987,672 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (4 hom., cov: 33)
  • Exomes 𝑓: 0.00020 (0 hom.)
• Consequence: HMCN2 NM_001291815.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.51

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

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 9-130391304-G-A is Benign according to our data. Variant chr9-130391304-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2659596.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.51 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMCN2	NM_001291815.2	c.9768G>A	p.Pro3256Pro	synonymous_variant	64/98	ENST00000683500.2	NP_001278744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMCN2	ENST00000683500.2	c.9768G>A	p.Pro3256Pro	synonymous_variant	64/98		NM_001291815.2	ENSP00000508292.2
HMCN2	ENST00000624552.4	c.9768G>A	p.Pro3256Pro	synonymous_variant	64/98	5		ENSP00000485357.2
HMCN2	ENST00000487727.6	n.861G>A		non_coding_transcript_exon_variant	7/29	5		ENSP00000485578.1

Frequencies

GnomAD3 genomes AF: 0.00271 AC: 412 AN: 152214 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00890

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00222

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.000956

GnomAD4 exome AF: 0.000200 AC: 167 AN: 835340 Hom.: 0 Cov.: 30 AF XY: 0.000158 AC XY: 61 AN XY: 385834

Gnomad4 AFR exome AF: 0.00769

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000394

Gnomad4 OTH exome AF: 0.000400

GnomAD4 genome AF: 0.00271 AC: 413 AN: 152332 Hom.: 4 Cov.: 33 AF XY: 0.00258 AC XY: 192 AN XY: 74490

Gnomad4 AFR AF: 0.00890

Gnomad4 AMR AF: 0.00222

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000278 Hom.: 0

Bravo AF: 0.00337

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

HMCN2: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.40
DANN	Benign	0.88

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs551741312; hg19: chr9-133266691;