rs42531

Positions:

• chr7-94423351-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000297268.11(COL1A2):​c.2565+233G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 545,616 control chromosomes in the GnomAD database, including 22,970 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (5258 hom., cov: 31)
  • Exomes 𝑓: 0.30 (17712 hom.)
• Consequence: COL1A2 ENST00000297268.11 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00500

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 7-94423351-G-A is Benign according to our data. Variant chr7-94423351-G-A is described in ClinVar as [Benign]. Clinvar id is 1269568.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL1A2	NM_000089.4	c.2565+233G>A		intron_variant		ENST00000297268.11	NP_000080.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL1A2	ENST00000297268.11	c.2565+233G>A		intron_variant		1	NM_000089.4	ENSP00000297268	P1
COL1A2	ENST00000481570.5	n.881G>A		non_coding_transcript_exon_variant	1/8	2

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36000 AN: 151834 Hom.: 5260 Cov.: 31

Gnomad AFR AF: 0.0613

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.296 AC: 116582 AN: 393662 Hom.: 17712 Cov.: 4 AF XY: 0.296 AC XY: 62360 AN XY: 210742

Gnomad4 AFR exome AF: 0.0564

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.294

Gnomad4 EAS exome AF: 0.263

Gnomad4 SAS exome AF: 0.283

Gnomad4 FIN exome AF: 0.363

Gnomad4 NFE exome AF: 0.313

Gnomad4 OTH exome AF: 0.276

GnomAD4 genome AF: 0.237 AC: 35986 AN: 151954 Hom.: 5258 Cov.: 31 AF XY: 0.241 AC XY: 17927 AN XY: 74278

Gnomad4 AFR AF: 0.0611

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.255

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.230

Alfa AF: 0.265 Hom.: 741

Bravo AF: 0.220

Asia WGS AF: 0.232 AC: 805 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.0
DANN	Benign	0.39

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: rs42531; hg19: chr7-94052663;