7-94410098-C-G

Variant names:

• chr7-94410098-C-G
• rs2621208
• NM_000089.4:c.1036-144C>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.1036-144C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 883,766 control chromosomes in the GnomAD database, including 26,173 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5108 hom., cov: 32)
  • Exomes 𝑓: 0.23 (21065 hom.)
• Consequence: COL1A2 NM_000089.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.688
• Publications: 9 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=-0.85).
• BP6: Variant 7-94410098-C-G is Benign according to our data. Variant chr7-94410098-C-G is described in ClinVar as Benign. ClinVar VariationId is 1259637.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.477 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.1036-144C>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.1036-144C>G		intron	N/A	ENSP00000297268.6	P08123
	COL1A2	ENST00000959377.1		c.1036-144C>G		intron	N/A	ENSP00000629436.1
	COL1A2	ENST00000959379.1		c.1036-144C>G		intron	N/A	ENSP00000629438.1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37572 AN: 151962 Hom.: 5087 Cov.: 32

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.209

GnomAD4 exome AF: 0.228 AC: 167060 AN: 731686 Hom.: 21065 AF XY: 0.229 AC XY: 88051 AN XY: 384770

African (AFR) AF: 0.306 AC: 5728 AN: 18738

American (AMR) AF: 0.212 AC: 7375 AN: 34810

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 2842 AN: 20938

East Asian (EAS) AF: 0.498 AC: 16380 AN: 32900

South Asian (SAS) AF: 0.251 AC: 16354 AN: 65238

European-Finnish (FIN) AF: 0.271 AC: 12264 AN: 45212

Middle Eastern (MID) AF: 0.128 AC: 358 AN: 2806

European-Non Finnish (NFE) AF: 0.206 AC: 98003 AN: 474836

Other (OTH) AF: 0.214 AC: 7756 AN: 36208

GnomAD4 genome AF: 0.248 AC: 37640 AN: 152080 Hom.: 5108 Cov.: 32 AF XY: 0.250 AC XY: 18548 AN XY: 74304

African (AFR) AF: 0.305 AC: 12642 AN: 41486

American (AMR) AF: 0.183 AC: 2795 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 482 AN: 3468

East Asian (EAS) AF: 0.493 AC: 2544 AN: 5160

South Asian (SAS) AF: 0.269 AC: 1295 AN: 4816

European-Finnish (FIN) AF: 0.288 AC: 3038 AN: 10566

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14085 AN: 67986

Other (OTH) AF: 0.217 AC: 457 AN: 2110

Alfa AF: 0.233 Hom.: 538

Bravo AF: 0.244

Asia WGS AF: 0.402 AC: 1398 AN: 3478

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	-0.85
CADD	Benign	0.73
DANN	Benign	0.71
PhyloP100		-0.69
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: rs2621208; hg19: chr7-94039410; COSMIC: COSV51955129; COSMIC: COSV51955129;