rs2318334

Positions:

• chr8-138777895-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152888.3(COL22A1):​c.1758+458A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 183,712 control chromosomes in the GnomAD database, including 8,935 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.30 (7629 hom., cov: 33)
  • Exomes 𝑓: 0.27 (1306 hom.)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338

Genes affected

COL22A1 (HGNC:22989): (collagen type XXII alpha 1 chain) This gene encodes member of the collagen family which is thought to contribute to the stabilization of myotendinous junctions and strengthen skeletal muscle attachments during contractile activity. It belongs to the fibril-associated collagens with interrupted triple helix (FACIT) subset of the collagen superfamily, which associate with collagen fibers through their C-terminal collagenous domains and mediate protein-protein interactions through their N-terminal noncollagenous domains. The encoded protein is deposited in the basement membrane zone of the myotendinous junction which is present only at the tissue junctions of muscles, tendons, the heart, articular cartilage, and skin. A knockdown of the orthologous zebrafish gene induces a muscular dystrophy by disruption of the myotendinous junction. [provided by RefSeq, May 2017]

COL22A1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL22A1	NM_152888.3	c.1758+458A>G		intron_variant		ENST00000303045.11	NP_690848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL22A1	ENST00000303045.11	c.1758+458A>G		intron_variant		1	NM_152888.3	ENSP00000303153.6
COL22A1	ENST00000522546.1	c.*368A>G		downstream_gene_variant		3		ENSP00000428244.1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 45995 AN: 151954 Hom.: 7616 Cov.: 33

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.279

GnomAD4 exome AF: 0.268 AC: 8483 AN: 31640 Hom.: 1306 Cov.: 0 AF XY: 0.273 AC XY: 4532 AN XY: 16580

Gnomad4 AFR exome AF: 0.428

Gnomad4 AMR exome AF: 0.293

Gnomad4 ASJ exome AF: 0.208

Gnomad4 EAS exome AF: 0.111

Gnomad4 SAS exome AF: 0.359

Gnomad4 FIN exome AF: 0.192

Gnomad4 NFE exome AF: 0.251

Gnomad4 OTH exome AF: 0.260

GnomAD4 genome AF: 0.303 AC: 46042 AN: 152072 Hom.: 7629 Cov.: 33 AF XY: 0.301 AC XY: 22353 AN XY: 74346

Gnomad4 AFR AF: 0.427

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.275

Alfa AF: 0.284 Hom.: 3885

Bravo AF: 0.312

Asia WGS AF: 0.247 AC: 857 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2318334; hg19: chr8-139790138;