7-94403441-A-G

Position:

• chr7-94403441-A-G

Variant summary

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

The NM_000089.4(COL1A2):​c.280-1115A>G variant causes a intron change. The variant allele was found at a frequency of 0.32 in 152,044 control chromosomes in the GnomAD database, including 8,751 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 0.32 (8751 hom., cov: 33)
• Consequence: COL1A2 NM_000089.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.96

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=-0.67).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL1A2	NM_000089.4	c.280-1115A>G		intron_variant		ENST00000297268.11	NP_000080.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL1A2	ENST00000297268.11	c.280-1115A>G		intron_variant		1	NM_000089.4	ENSP00000297268	P1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48605 AN: 151926 Hom.: 8751 Cov.: 33

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.320 AC: 48604 AN: 152044 Hom.: 8751 Cov.: 33 AF XY: 0.326 AC XY: 24258 AN XY: 74316

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.312

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.445

Gnomad4 FIN AF: 0.540

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.289

Alfa AF: 0.352 Hom.: 17667

Bravo AF: 0.292

Asia WGS AF: 0.386 AC: 1337 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	14
DANN	Benign	0.64

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: rs1858822; hg19: chr7-94032753;