Variant chr7-94417954-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000089.4(COL1A2):c.1971+123C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0506 in 797,364 control chromosomes in the GnomAD database, including 4,062 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.084 ( 1266 hom., cov: 32)

Exomes 𝑓: 0.043 ( 2796 hom. )

Consequence

COL1A2
NM_000089.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.132

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 7-94417954-C-A is Benign according to our data. Variant chr7-94417954-C-A is described in ClinVar as [Benign]. Clinvar id is 678062.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.36 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.1971+123C>A		intron_variant		ENST00000297268.11

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
COL1A2	ENST00000297268.11 linkuse as main transcript	c.1971+123C>A	intron_variant	1	NM_000089.4	P1
COL1A2	ENST00000461525.5 linkuse as main transcript	n.60+123C>A	intron_variant, non_coding_transcript_variant	1
COL1A2	ENST00000473573.5 linkuse as main transcript	n.308+123C>A	intron_variant, non_coding_transcript_variant	2
COL1A2	ENST00000497316.5 linkuse as main transcript	n.368+123C>A	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0840

AC:

12759

AN:

151908

Hom.:

1257

Cov.:

show subpopulations

Gnomad AFR

AF:

0.200

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0655

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.375

Gnomad SAS

AF:

0.0683

Gnomad FIN

AF:

0.0323

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0102

Gnomad OTH

AF:

0.0758

GnomAD4 exome

AF:

0.0427

AC:

27569

AN:

645338

Hom.:

2796

AF XY:

0.0416

AC XY:

14256

AN XY:

342792

show subpopulations

Gnomad4 AFR exome

AF:

0.196

Gnomad4 AMR exome

AF:

0.0685

Gnomad4 ASJ exome

AF:

0.0143

Gnomad4 EAS exome

AF:

0.356

Gnomad4 SAS exome

AF:

0.0536

Gnomad4 FIN exome

AF:

0.0314

Gnomad4 NFE exome

AF:

0.00952

Gnomad4 OTH exome

AF:

0.0495

GnomAD4 genome

AF:

0.0842

AC:

12800

AN:

152026

Hom.:

1266

Cov.:

AF XY:

0.0853

AC XY:

6339

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.200

Gnomad4 AMR

AF:

0.0656

Gnomad4 ASJ

AF:

0.0138

Gnomad4 EAS

AF:

0.374

Gnomad4 SAS

AF:

0.0680

Gnomad4 FIN

AF:

0.0323

Gnomad4 NFE

AF:

0.0102

Gnomad4 OTH

AF:

0.0802

Alfa

AF:

0.0286

Hom.:

465

Bravo

AF:

0.0934

Asia WGS

AF:

0.238

AC:

828

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

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

-0.84

CADD

Benign

1.5

DANN

Benign

0.51

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