chr7-94401587-T-C

Position:

chr7-94401587-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000089.4(COL1A2):c.246T>C(p.Asp82=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 1,560,246 control chromosomes in the GnomAD database, including 24,919 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 6961 hom., cov: 30)

Exomes 𝑓: 0.14 ( 17958 hom. )

Consequence

COL1A2
NM_000089.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.38

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 7-94401587-T-C is Benign according to our data. Variant chr7-94401587-T-C is described in ClinVar as [Benign]. Clinvar id is 254955.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-94401587-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.38 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.511 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.246T>C	p.Asp82=	synonymous_variant	6/52	ENST00000297268.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL1A2	ENST00000297268.11 linkuse as main transcript	c.246T>C	p.Asp82=	synonymous_variant	6/52	1	NM_000089.4	P1

Frequencies

GnomAD3 genomes

AF:

0.245

AC:

36909

AN:

150588

Hom.:

6937

Cov.:

show subpopulations

Gnomad AFR

AF:

0.516

Gnomad AMI

AF:

0.100

Gnomad AMR

AF:

0.177

Gnomad ASJ

AF:

0.156

Gnomad EAS

AF:

0.405

Gnomad SAS

AF:

0.0980

Gnomad FIN

AF:

0.105

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.122

Gnomad OTH

AF:

0.236

GnomAD3 exomes

AF:

0.165

AC:

40326

AN:

245108

Hom.:

5144

AF XY:

0.153

AC XY:

20382

AN XY:

132812

show subpopulations

Gnomad AFR exome

AF:

0.525

Gnomad AMR exome

AF:

0.133

Gnomad ASJ exome

AF:

0.149

Gnomad EAS exome

AF:

0.390

Gnomad SAS exome

AF:

0.0849

Gnomad FIN exome

AF:

0.111

Gnomad NFE exome

AF:

0.121

Gnomad OTH exome

AF:

0.154

GnomAD4 exome

AF:

0.137

AC:

193444

AN:

1409550

Hom.:

17958

Cov.:

AF XY:

0.134

AC XY:

94138

AN XY:

700838

show subpopulations

Gnomad4 AFR exome

AF:

0.522

Gnomad4 AMR exome

AF:

0.138

Gnomad4 ASJ exome

AF:

0.145

Gnomad4 EAS exome

AF:

0.426

Gnomad4 SAS exome

AF:

0.0842

Gnomad4 FIN exome

AF:

0.111

Gnomad4 NFE exome

AF:

0.119

Gnomad4 OTH exome

AF:

0.162

GnomAD4 genome

AF:

0.245

AC:

36975

AN:

150696

Hom.:

6961

Cov.:

AF XY:

0.242

AC XY:

17812

AN XY:

73636

show subpopulations

Gnomad4 AFR

AF:

0.516

Gnomad4 AMR

AF:

0.176

Gnomad4 ASJ

AF:

0.156

Gnomad4 EAS

AF:

0.404

Gnomad4 SAS

AF:

0.0985

Gnomad4 FIN

AF:

0.105

Gnomad4 NFE

AF:

0.122

Gnomad4 OTH

AF:

0.239

Alfa

AF:

0.150

Hom.:

3368

Bravo

AF:

0.267

Asia WGS

AF:

0.292

AC:

1010

AN:

3462

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 22, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 28, 2017	- -

Osteogenesis imperfecta

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Ehlers-danlos syndrome, arthrochalasia type, 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Osteogenesis imperfecta type I;C0268335:Ehlers-Danlos syndrome, classic type, 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 04, 2018

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.48

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