rs2521205

Positions:

• chr7-94417229-G-T

Variant summary

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

The NM_000089.4(COL1A2):​c.1864-495G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 151,898 control chromosomes in the GnomAD database, including 16,007 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 0.45 (16007 hom., cov: 32)
• Consequence: COL1A2 NM_000089.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.527

Genes affected

COL1A2 (HGNC:2198): (collagen type I alpha 2 chain) This gene encodes the pro-alpha2 chain of type I collagen whose triple helix comprises two alpha1 chains and one alpha2 chain. Type I is a fibril-forming collagen found in most connective tissues and is abundant in bone, cornea, dermis and tendon. Mutations in this gene are associated with osteogenesis imperfecta types I-IV, Ehlers-Danlos syndrome type VIIB, recessive Ehlers-Danlos syndrome Classical type, idiopathic osteoporosis, and atypical Marfan syndrome. Symptoms associated with mutations in this gene, however, tend to be less severe than mutations in the gene for the alpha1 chain of type I collagen (COL1A1) reflecting the different role of alpha2 chains in matrix integrity. Three transcripts, resulting from the use of alternate polyadenylation signals, have been identified for this gene. [provided by R. Dalgleish, Feb 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL1A2	NM_000089.4	c.1864-495G>T		intron_variant		ENST00000297268.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL1A2	ENST00000297268.11	c.1864-495G>T		intron_variant		1	NM_000089.4	P1
COL1A2	ENST00000473573.5	n.201-495G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68858 AN: 151780 Hom.: 15989 Cov.: 32

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.445

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.454 AC: 68929 AN: 151898 Hom.: 16007 Cov.: 32 AF XY: 0.448 AC XY: 33247 AN XY: 74234

Gnomad4 AFR AF: 0.393

Gnomad4 AMR AF: 0.520

Gnomad4 ASJ AF: 0.432

Gnomad4 EAS AF: 0.284

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.501

Gnomad4 OTH AF: 0.445

Alfa AF: 0.493 Hom.: 24919

Bravo AF: 0.462

Asia WGS AF: 0.330 AC: 1145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.9
DANN	Benign	0.41

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: rs2521205; hg19: chr7-94046541;