rs411717

chr7-94403719-T-C

Variant summary

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

The NM_000089.4(COL1A2):c.280-837T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 151,962 control chromosomes in the GnomAD database, including 19,754 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 0.50 (19754 hom., cov: 32)
• Consequence: COL1A2 NM_000089.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.762

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL1A2	NM_000089.4	c.280-837T>C		intron_variant		ENST00000297268.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL1A2	ENST00000297268.11	c.280-837T>C		intron_variant		1	NM_000089.4	P1

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75427 AN: 151844 Hom.: 19748 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.478

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

GnomAD4 genome AF: 0.497 AC: 75455 AN: 151962 Hom.: 19754 Cov.: 32 AF XY: 0.500 AC XY: 37132 AN XY: 74266

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.569

Gnomad4 ASJ AF: 0.473

Gnomad4 EAS AF: 0.509

Gnomad4 SAS AF: 0.551

Gnomad4 FIN AF: 0.618

Gnomad4 NFE AF: 0.565

Gnomad4 OTH AF: 0.477

Alfa AF: 0.544 Hom.: 33467

Bravo AF: 0.485

Asia WGS AF: 0.498 AC: 1729 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	14
Dann	Benign	0.69

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: rs411717; hg19: chr7-94033031;