rs2521206

chr7-94409875-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000089.4(COL1A2):c.1035+54A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 1,510,184 control chromosomes in the GnomAD database, including 41,184 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (5152 hom., cov: 32)
  • Exomes 𝑓: 0.22 (36032 hom.)
• Consequence: COL1A2 NM_000089.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.795

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 7-94409875-A-G is Benign according to our data. Variant chr7-94409875-A-G is described in ClinVar as [Benign]. Clinvar id is 675065.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL1A2	NM_000089.4	c.1035+54A>G		intron_variant		ENST00000297268.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL1A2	ENST00000297268.11	c.1035+54A>G		intron_variant		1	NM_000089.4	P1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37686 AN: 151844 Hom.: 5129 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.208

GnomAD4 exome AF: 0.223 AC: 303124 AN: 1358222 Hom.: 36032 AF XY: 0.223 AC XY: 152161 AN XY: 681342

Gnomad4 AFR exome AF: 0.312

Gnomad4 AMR exome AF: 0.215

Gnomad4 ASJ exome AF: 0.137

Gnomad4 EAS exome AF: 0.494

Gnomad4 SAS exome AF: 0.252

Gnomad4 FIN exome AF: 0.273

Gnomad4 NFE exome AF: 0.208

Gnomad4 OTH exome AF: 0.216

GnomAD4 genome AF: 0.248 AC: 37756 AN: 151962 Hom.: 5152 Cov.: 32 AF XY: 0.251 AC XY: 18624 AN XY: 74270

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.493

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.216

Alfa AF: 0.207 Hom.: 4561

Bravo AF: 0.245

Asia WGS AF: 0.404 AC: 1404 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	4.7
Dann	Benign	0.37

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: rs2521206; hg19: chr7-94039187; COSMIC: COSV51953123; COSMIC: COSV51953123;