rs42522

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_000089.4(COL1A2):​c.1351-417G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 152,132 control chromosomes in the GnomAD database, including 46,767 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 0.78 ( 46767 hom., cov: 32)

Consequence

COL1A2
NM_000089.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.22
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
COL1A2NM_000089.4 linkc.1351-417G>A intron_variant ENST00000297268.11 NP_000080.2 P08123A0A0S2Z3H5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
COL1A2ENST00000297268.11 linkc.1351-417G>A intron_variant 1 NM_000089.4 ENSP00000297268.6 P08123

Frequencies

GnomAD3 genomes
AF:
0.782
AC:
118901
AN:
152016
Hom.:
46719
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.814
Gnomad AMI
AF:
0.700
Gnomad AMR
AF:
0.793
Gnomad ASJ
AF:
0.666
Gnomad EAS
AF:
0.906
Gnomad SAS
AF:
0.662
Gnomad FIN
AF:
0.784
Gnomad MID
AF:
0.653
Gnomad NFE
AF:
0.768
Gnomad OTH
AF:
0.742
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.782
AC:
119008
AN:
152132
Hom.:
46767
Cov.:
32
AF XY:
0.780
AC XY:
58047
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.814
Gnomad4 AMR
AF:
0.792
Gnomad4 ASJ
AF:
0.666
Gnomad4 EAS
AF:
0.906
Gnomad4 SAS
AF:
0.662
Gnomad4 FIN
AF:
0.784
Gnomad4 NFE
AF:
0.768
Gnomad4 OTH
AF:
0.744
Alfa
AF:
0.742
Hom.:
3397
Bravo
AF:
0.787

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.46
CADD
Benign
16
DANN
Benign
0.67

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs42522; hg19: chr7-94040963; API