dbSNP rs2301643: COL1A2:c.1666-41G>A (chr7-94414181-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000089.4(COL1A2):c.1666-41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 1,603,114 control chromosomes in the GnomAD database, including 28,298 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2416 hom., cov: 32)

Exomes 𝑓: 0.18 ( 25882 hom. )

Consequence

COL1A2
NM_000089.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.60

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]

COL1A2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 7-94414181-G-A is Benign according to our data. Variant chr7-94414181-G-A is described in ClinVar as [Benign]. Clinvar id is 674830.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL1A2	NM_000089.4 link	c.1666-41G>A		intron_variant	Intron 28 of 51	ENST00000297268.11	NP_000080.2	P08123A0A0S2Z3H5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL1A2	ENST00000297268.11 link	c.1666-41G>A	intron_variant	Intron 28 of 51	1	NM_000089.4	ENSP00000297268.6	P08123
COL1A2	ENST00000488298.5 link	n.90-41G>A	intron_variant	Intron 2 of 4	2
COL1A2	ENST00000473573.5 link	n.-39G>A	upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.172

AC:

26069

AN:

151968

Hom.:

2412

Cov.:

show subpopulations

Gnomad AFR

AF:

0.141

Gnomad AMI

AF:

0.0724

Gnomad AMR

AF:

0.285

Gnomad ASJ

AF:

0.163

Gnomad EAS

AF:

0.115

Gnomad SAS

AF:

0.106

Gnomad FIN

AF:

0.0854

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.188

Gnomad OTH

AF:

0.187

GnomAD3 exomes

AF:

0.183

AC:

45784

AN:

250562

Hom.:

4986

AF XY:

0.175

AC XY:

23680

AN XY:

135416

show subpopulations

Gnomad AFR exome

AF:

0.139

Gnomad AMR exome

AF:

0.347

Gnomad ASJ exome

AF:

0.179

Gnomad EAS exome

AF:

0.126

Gnomad SAS exome

AF:

0.104

Gnomad FIN exome

AF:

0.0993

Gnomad NFE exome

AF:

0.185

Gnomad OTH exome

AF:

0.188

GnomAD4 exome

AF:

0.184

AC:

267454

AN:

1451028

Hom.:

25882

Cov.:

AF XY:

0.181

AC XY:

130814

AN XY:

722608

show subpopulations

Gnomad4 AFR exome

AF:

0.139

Gnomad4 AMR exome

AF:

0.341

Gnomad4 ASJ exome

AF:

0.181

Gnomad4 EAS exome

AF:

0.104

Gnomad4 SAS exome

AF:

0.108

Gnomad4 FIN exome

AF:

0.107

Gnomad4 NFE exome

AF:

0.193

Gnomad4 OTH exome

AF:

0.178

GnomAD4 genome

AF:

0.172

AC:

26091

AN:

152086

Hom.:

2416

Cov.:

AF XY:

0.169

AC XY:

12537

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.141

Gnomad4 AMR

AF:

0.285

Gnomad4 ASJ

AF:

0.163

Gnomad4 EAS

AF:

0.115

Gnomad4 SAS

AF:

0.108

Gnomad4 FIN

AF:

0.0854

Gnomad4 NFE

AF:

0.188

Gnomad4 OTH

AF:

0.185

Alfa

AF:

0.124

Hom.:

259

Bravo

AF:

0.187

Asia WGS

AF:

0.114

AC:

396

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

7.5

DANN

Benign

0.63

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over