dbSNP rs42530: COL1A2:c.2565+65A>G (chr7-94423183-A-G) – 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.2565+65A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 1,577,000 control chromosomes in the GnomAD database, including 70,474 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 5290 hom., cov: 32)

Exomes 𝑓: 0.30 ( 65184 hom. )

Consequence

COL1A2
NM_000089.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.399

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 7-94423183-A-G is Benign according to our data. Variant chr7-94423183-A-G is described in ClinVar as [Benign]. Clinvar id is 674831.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL1A2	NM_000089.4 link	c.2565+65A>G		intron_variant	Intron 40 of 51	ENST00000297268.11	NP_000080.2	P08123A0A0S2Z3H5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL1A2	ENST00000297268.11 link	c.2565+65A>G	intron_variant	Intron 40 of 51	1	NM_000089.4	ENSP00000297268.6	P08123
COL1A2	ENST00000481570.5 link	n.713A>G	non_coding_transcript_exon_variant	Exon 1 of 8	2
COL1A2	ENST00000497316.5 link	n.*65A>G	downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.238

AC:

36110

AN:

152008

Hom.:

5292

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0614

Gnomad AMI

AF:

0.283

Gnomad AMR

AF:

0.257

Gnomad ASJ

AF:

0.283

Gnomad EAS

AF:

0.257

Gnomad SAS

AF:

0.281

Gnomad FIN

AF:

0.379

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.311

Gnomad OTH

AF:

0.234

GnomAD4 exome

AF:

0.299

AC:

425711

AN:

1424874

Hom.:

65184

Cov.:

AF XY:

0.300

AC XY:

213180

AN XY:

710876

show subpopulations

Gnomad4 AFR exome

AF:

0.0478

Gnomad4 AMR exome

AF:

0.243

Gnomad4 ASJ exome

AF:

0.291

Gnomad4 EAS exome

AF:

0.259

Gnomad4 SAS exome

AF:

0.286

Gnomad4 FIN exome

AF:

0.366

Gnomad4 NFE exome

AF:

0.309

Gnomad4 OTH exome

AF:

0.281

GnomAD4 genome

AF:

0.237

AC:

36097

AN:

152126

Hom.:

5290

Cov.:

AF XY:

0.242

AC XY:

17997

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0612

Gnomad4 AMR

AF:

0.258

Gnomad4 ASJ

AF:

0.283

Gnomad4 EAS

AF:

0.257

Gnomad4 SAS

AF:

0.280

Gnomad4 FIN

AF:

0.379

Gnomad4 NFE

AF:

0.311

Gnomad4 OTH

AF:

0.231

Alfa

AF:

0.296

Hom.:

9835

Bravo

AF:

0.221

Asia WGS

AF:

0.232

AC:

806

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 18, 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

5.7

DANN

Benign

0.71

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