dbSNP rs42526: COL1A2:c.1765-141G>A (chr7-94416264-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.1765-141G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.699 in 680,802 control chromosomes in the GnomAD database, including 169,210 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 34060 hom., cov: 33)

Exomes 𝑓: 0.71 ( 135150 hom. )

Consequence

COL1A2
NM_000089.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.90

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 7-94416264-G-A is Benign according to our data. Variant chr7-94416264-G-A is described in ClinVar as [Benign]. Clinvar id is 1247190.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL1A2	NM_000089.4 link	c.1765-141G>A		intron_variant	Intron 30 of 51	ENST00000297268.11	NP_000080.2	P08123A0A0S2Z3H5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL1A2	ENST00000297268.11 link	c.1765-141G>A	intron_variant	Intron 30 of 51	1	NM_000089.4	ENSP00000297268.6	P08123
COL1A2	ENST00000473573.5 link	n.102-141G>A	intron_variant	Intron 2 of 10	2
COL1A2	ENST00000488298.5 link	n.189-141G>A	intron_variant	Intron 4 of 4	2

Frequencies

GnomAD3 genomes

AF:

0.660

AC:

100302

AN:

152042

Hom.:

34043

Cov.:

show subpopulations

Gnomad AFR

AF:

0.495

Gnomad AMI

AF:

0.700

Gnomad AMR

AF:

0.716

Gnomad ASJ

AF:

0.655

Gnomad EAS

AF:

0.540

Gnomad SAS

AF:

0.592

Gnomad FIN

AF:

0.751

Gnomad MID

AF:

0.611

Gnomad NFE

AF:

0.748

Gnomad OTH

AF:

0.633

GnomAD4 exome

AF:

0.710

AC:

375484

AN:

528642

Hom.:

135150

AF XY:

0.704

AC XY:

194751

AN XY:

276472

show subpopulations

Gnomad4 AFR exome

AF:

0.487

Gnomad4 AMR exome

AF:

0.735

Gnomad4 ASJ exome

AF:

0.657

Gnomad4 EAS exome

AF:

0.584

Gnomad4 SAS exome

AF:

0.584

Gnomad4 FIN exome

AF:

0.751

Gnomad4 NFE exome

AF:

0.749

Gnomad4 OTH exome

AF:

0.683

GnomAD4 genome

AF:

0.660

AC:

100358

AN:

152160

Hom.:

34060

Cov.:

AF XY:

0.658

AC XY:

48912

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.495

Gnomad4 AMR

AF:

0.716

Gnomad4 ASJ

AF:

0.655

Gnomad4 EAS

AF:

0.540

Gnomad4 SAS

AF:

0.593

Gnomad4 FIN

AF:

0.751

Gnomad4 NFE

AF:

0.748

Gnomad4 OTH

AF:

0.630

Alfa

AF:

0.627

Hom.:

2178

Bravo

AF:

0.652

Asia WGS

AF:

0.550

AC:

1911

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

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

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