dbSNP rs34026686: COL1A2:c.1251+33G>A (chr7-94410975-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.1251+33G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,612,312 control chromosomes in the GnomAD database, including 30,293 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2375 hom., cov: 30)

Exomes 𝑓: 0.19 ( 27918 hom. )

Consequence

COL1A2
NM_000089.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.408

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=-0.85).

BP6

Variant 7-94410975-G-A is Benign according to our data. Variant chr7-94410975-G-A is described in ClinVar as [Benign]. Clinvar id is 674829.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL1A2	NM_000089.4 link	c.1251+33G>A		intron_variant	Intron 22 of 51	ENST00000297268.11	NP_000080.2	P08123A0A0S2Z3H5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL1A2	ENST00000297268.11 link	c.1251+33G>A		intron_variant	Intron 22 of 51	1	NM_000089.4	ENSP00000297268.6		P08123

Frequencies

GnomAD3 genomes

AF:

0.167

AC:

25304

AN:

151602

Hom.:

2369

Cov.:

show subpopulations

Gnomad AFR

AF:

0.108

Gnomad AMI

AF:

0.0728

Gnomad AMR

AF:

0.296

Gnomad ASJ

AF:

0.163

Gnomad EAS

AF:

0.111

Gnomad SAS

AF:

0.104

Gnomad FIN

AF:

0.0847

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.196

Gnomad OTH

AF:

0.188

GnomAD3 exomes

AF:

0.185

AC:

46502

AN:

251272

Hom.:

5232

AF XY:

0.178

AC XY:

24160

AN XY:

135818

show subpopulations

Gnomad AFR exome

AF:

0.107

Gnomad AMR exome

AF:

0.354

Gnomad ASJ exome

AF:

0.178

Gnomad EAS exome

AF:

0.122

Gnomad SAS exome

AF:

0.104

Gnomad FIN exome

AF:

0.0990

Gnomad NFE exome

AF:

0.194

Gnomad OTH exome

AF:

0.190

GnomAD4 exome

AF:

0.190

AC:

278089

AN:

1460598

Hom.:

27918

Cov.:

AF XY:

0.187

AC XY:

135776

AN XY:

726660

show subpopulations

Gnomad4 AFR exome

AF:

0.104

Gnomad4 AMR exome

AF:

0.348

Gnomad4 ASJ exome

AF:

0.178

Gnomad4 EAS exome

AF:

0.102

Gnomad4 SAS exome

AF:

0.107

Gnomad4 FIN exome

AF:

0.107

Gnomad4 NFE exome

AF:

0.201

Gnomad4 OTH exome

AF:

0.182

GnomAD4 genome

AF:

0.167

AC:

25330

AN:

151714

Hom.:

2375

Cov.:

AF XY:

0.165

AC XY:

12206

AN XY:

74090

show subpopulations

Gnomad4 AFR

AF:

0.108

Gnomad4 AMR

AF:

0.296

Gnomad4 ASJ

AF:

0.163

Gnomad4 EAS

AF:

0.111

Gnomad4 SAS

AF:

0.106

Gnomad4 FIN

AF:

0.0847

Gnomad4 NFE

AF:

0.196

Gnomad4 OTH

AF:

0.186

Alfa

AF:

0.173

Hom.:

487

Bravo

AF:

0.182

Asia WGS

AF:

0.109

AC:

380

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 14, 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

-0.85

CADD

Benign

0.59

DANN

Benign

0.42

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