7-94426932-C-G

Variant names:

• chr7-94426932-C-G
• rs413826
• NM_000089.4:c.3106-76C>G

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.3106-76C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 1,344,478 control chromosomes in the GnomAD database, including 260,859 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (25227 hom., cov: 30)
  • Exomes 𝑓: 0.62 (235632 hom.)
• Consequence: COL1A2 NM_000089.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0690
• Publications: 11 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):

• COL1A2-related Ehlers-Danlos syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• COL1A2-related osteogenesis imperfecta

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Ehlers-Danlos syndrome, arthrochalasia type, 2

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

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

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

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

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

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

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

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• congenital heart disease

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 7-94426932-C-G is Benign according to our data. Variant chr7-94426932-C-G is described in ClinVar as Benign. ClinVar VariationId is 674833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000089.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL1A2	NM_000089.4	MANE Select	c.3106-76C>G		intron	N/A	NP_000080.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL1A2	ENST00000297268.11	TSL:1 MANE Select	c.3106-76C>G		intron	N/A	ENSP00000297268.6	P08123
	COL1A2	ENST00000959377.1		c.3103-76C>G		intron	N/A	ENSP00000629436.1
	COL1A2	ENST00000959379.1		c.3106-76C>G		intron	N/A	ENSP00000629438.1

Frequencies

GnomAD3 genomes AF: 0.576 AC: 86329 AN: 149850 Hom.: 25214 Cov.: 30

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.540

GnomAD4 exome AF: 0.624 AC: 745028 AN: 1194518 Hom.: 235632 Cov.: 16 AF XY: 0.622 AC XY: 374991 AN XY: 603258

African (AFR) AF: 0.443 AC: 12454 AN: 28136

American (AMR) AF: 0.676 AC: 26869 AN: 39734

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 12849 AN: 23918

East Asian (EAS) AF: 0.503 AC: 19007 AN: 37776

South Asian (SAS) AF: 0.564 AC: 42750 AN: 75794

European-Finnish (FIN) AF: 0.668 AC: 34420 AN: 51532

Middle Eastern (MID) AF: 0.446 AC: 2090 AN: 4682

European-Non Finnish (NFE) AF: 0.640 AC: 564517 AN: 881650

Other (OTH) AF: 0.586 AC: 30072 AN: 51296

GnomAD4 genome AF: 0.576 AC: 86371 AN: 149960 Hom.: 25227 Cov.: 30 AF XY: 0.577 AC XY: 42189 AN XY: 73096

African (AFR) AF: 0.449 AC: 18192 AN: 40500

American (AMR) AF: 0.624 AC: 9475 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 1815 AN: 3462

East Asian (EAS) AF: 0.544 AC: 2558 AN: 4706

South Asian (SAS) AF: 0.565 AC: 2689 AN: 4760

European-Finnish (FIN) AF: 0.675 AC: 6955 AN: 10298

Middle Eastern (MID) AF: 0.466 AC: 136 AN: 292

European-Non Finnish (NFE) AF: 0.632 AC: 42857 AN: 67778

Other (OTH) AF: 0.538 AC: 1121 AN: 2082

Alfa AF: 0.593 Hom.: 3280

Bravo AF: 0.563

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.6
DANN	Benign	0.46
PhyloP100		0.069
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: rs413826; hg19: chr7-94056244; COSMIC: COSV107384989; COSMIC: COSV107384989;