Variant chr7-94409654-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000089.4(COL1A2):c.936+46G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,613,546 control chromosomes in the GnomAD database, including 11,511 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2022 hom., cov: 33)

Exomes 𝑓: 0.11 ( 9489 hom. )

Consequence

COL1A2
NM_000089.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.656

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 7-94409654-G-A is Benign according to our data. Variant chr7-94409654-G-A is described in ClinVar as [Benign]. Clinvar id is 674979.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL1A2	NM_000089.4 linkuse as main transcript	c.936+46G>A		intron_variant		ENST00000297268.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL1A2	ENST00000297268.11 linkuse as main transcript	c.936+46G>A		intron_variant		1	NM_000089.4	P1

Frequencies

GnomAD3 genomes

AF:

0.147

AC:

22328

AN:

152048

Hom.:

2015

Cov.:

show subpopulations

Gnomad AFR

AF:

0.259

Gnomad AMI

AF:

0.0998

Gnomad AMR

AF:

0.115

Gnomad ASJ

AF:

0.139

Gnomad EAS

AF:

0.0426

Gnomad SAS

AF:

0.0292

Gnomad FIN

AF:

0.0776

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.114

Gnomad OTH

AF:

0.143

GnomAD3 exomes

AF:

0.101

AC:

25408

AN:

251450

Hom.:

1687

AF XY:

0.0967

AC XY:

13138

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.262

Gnomad AMR exome

AF:

0.0807

Gnomad ASJ exome

AF:

0.131

Gnomad EAS exome

AF:

0.0362

Gnomad SAS exome

AF:

0.0310

Gnomad FIN exome

AF:

0.0803

Gnomad NFE exome

AF:

0.114

Gnomad OTH exome

AF:

0.116

GnomAD4 exome

AF:

0.109

AC:

159563

AN:

1461380

Hom.:

9489

Cov.:

AF XY:

0.106

AC XY:

77412

AN XY:

727020

show subpopulations

Gnomad4 AFR exome

AF:

0.260

Gnomad4 AMR exome

AF:

0.0859

Gnomad4 ASJ exome

AF:

0.129

Gnomad4 EAS exome

AF:

0.0783

Gnomad4 SAS exome

AF:

0.0321

Gnomad4 FIN exome

AF:

0.0832

Gnomad4 NFE exome

AF:

0.113

Gnomad4 OTH exome

AF:

0.114

GnomAD4 genome

AF:

0.147

AC:

22358

AN:

152166

Hom.:

2022

Cov.:

AF XY:

0.141

AC XY:

10520

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.259

Gnomad4 AMR

AF:

0.115

Gnomad4 ASJ

AF:

0.139

Gnomad4 EAS

AF:

0.0427

Gnomad4 SAS

AF:

0.0299

Gnomad4 FIN

AF:

0.0776

Gnomad4 NFE

AF:

0.114

Gnomad4 OTH

AF:

0.142

Alfa

AF:

0.131

Hom.:

298

Bravo

AF:

0.157

Asia WGS

AF:

0.0520

AC:

181

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2018	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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.2

DANN

Benign

0.58

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