7-94426732-G-T

Variant names:

• chr7-94426732-G-T
• rs2621215
• NM_000089.4:c.3105+202G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000089.4(COL1A2):​c.3105+202G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.764 in 642,502 control chromosomes in the GnomAD database, including 188,575 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (43805 hom., cov: 31)
  • Exomes 𝑓: 0.77 (144770 hom.)
• Consequence: COL1A2 NM_000089.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.250
• Publications: 20 publications found

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 Gene-Disease associations (from GenCC):

• Ehlers-Danlos syndrome, arthrochalasia type, 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Illumina, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• osteogenesis imperfecta

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• osteogenesis imperfecta type 1

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• osteogenesis imperfecta type 2

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P, ClinGen
• osteogenesis imperfecta type 3

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen
• osteogenesis imperfecta type 4

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Ehlers-Danlos syndrome, arthrochalasia type

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen
• Ehlers-Danlos syndrome, cardiac valvular type

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, ClinGen, PanelApp Australia, Orphanet, G2P
• combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen, Ambry Genetics
• Ehlers-Danlos/osteogenesis imperfecta syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• high bone mass osteogenesis imperfecta

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 7-94426732-G-T is Benign according to our data. Variant chr7-94426732-G-T is described in ClinVar as Benign. ClinVar VariationId is 1268257.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL1A2	NM_000089.4	c.3105+202G>T		intron_variant	Intron 46 of 51	ENST00000297268.11	NP_000080.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL1A2	ENST00000297268.11	c.3105+202G>T		intron_variant	Intron 46 of 51	1	NM_000089.4	ENSP00000297268.6

Frequencies

GnomAD3 genomes AF: 0.758 AC: 115051 AN: 151846 Hom.: 43763 Cov.: 31

Gnomad AFR AF: 0.715

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.798

Gnomad ASJ AF: 0.710

Gnomad EAS AF: 0.907

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.650

Gnomad NFE AF: 0.767

Gnomad OTH AF: 0.731

GnomAD4 exome AF: 0.765 AC: 375429 AN: 490538 Hom.: 144770 Cov.: 5 AF XY: 0.758 AC XY: 198994 AN XY: 262368

African (AFR) AF: 0.709 AC: 9423 AN: 13298

American (AMR) AF: 0.825 AC: 19420 AN: 23526

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 10834 AN: 15204

East Asian (EAS) AF: 0.932 AC: 29501 AN: 31652

South Asian (SAS) AF: 0.656 AC: 31917 AN: 48686

European-Finnish (FIN) AF: 0.787 AC: 24938 AN: 31684

Middle Eastern (MID) AF: 0.656 AC: 1540 AN: 2346

European-Non Finnish (NFE) AF: 0.766 AC: 227066 AN: 296402

Other (OTH) AF: 0.749 AC: 20790 AN: 27740

GnomAD4 genome AF: 0.758 AC: 115151 AN: 151964 Hom.: 43805 Cov.: 31 AF XY: 0.757 AC XY: 56263 AN XY: 74302

African (AFR) AF: 0.715 AC: 29572 AN: 41366

American (AMR) AF: 0.798 AC: 12187 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.710 AC: 2461 AN: 3466

East Asian (EAS) AF: 0.907 AC: 4690 AN: 5172

South Asian (SAS) AF: 0.669 AC: 3224 AN: 4816

European-Finnish (FIN) AF: 0.792 AC: 8379 AN: 10578

Middle Eastern (MID) AF: 0.661 AC: 193 AN: 292

European-Non Finnish (NFE) AF: 0.767 AC: 52159 AN: 67976

Other (OTH) AF: 0.732 AC: 1547 AN: 2112

Alfa AF: 0.762 Hom.: 62265

Bravo AF: 0.759

Asia WGS AF: 0.793 AC: 2757 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	-0.90
CADD	Benign	7.5
DANN	Benign	0.56
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2621215; hg19: chr7-94056044;