rs7804898

Positions:

• chr7-94426787-A-G

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_000089.4(COL1A2):​c.3106-221A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 626,086 control chromosomes in the GnomAD database, including 5,412 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1034 hom., cov: 31)
  • Exomes 𝑓: 0.13 (4378 hom.)
• Consequence: COL1A2 NM_000089.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.63

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 7-94426787-A-G is Benign according to our data. Variant chr7-94426787-A-G is described in ClinVar as [Benign]. Clinvar id is 1221203.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL1A2	NM_000089.4	c.3106-221A>G		intron_variant		ENST00000297268.11	NP_000080.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL1A2	ENST00000297268.11	c.3106-221A>G		intron_variant		1	NM_000089.4	ENSP00000297268.6
COL1A2	ENST00000481570.5	n.3335A>G		non_coding_transcript_exon_variant	5/8	2
COL1A2	ENST00000492110.1	n.5A>G		non_coding_transcript_exon_variant	1/2	2
COL1A2	ENST00000488121.1	n.22-221A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16384 AN: 152064 Hom.: 1033 Cov.: 31

Gnomad AFR AF: 0.0594

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.0583

Gnomad ASJ AF: 0.0817

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.0750

GnomAD4 exome AF: 0.129 AC: 60996 AN: 473904 Hom.: 4378 Cov.: 5 AF XY: 0.131 AC XY: 33179 AN XY: 253080

Gnomad4 AFR exome AF: 0.0612

Gnomad4 AMR exome AF: 0.0716

Gnomad4 ASJ exome AF: 0.0700

Gnomad4 EAS exome AF: 0.137

Gnomad4 SAS exome AF: 0.168

Gnomad4 FIN exome AF: 0.184

Gnomad4 NFE exome AF: 0.128

Gnomad4 OTH exome AF: 0.109

GnomAD4 genome AF: 0.108 AC: 16401 AN: 152182 Hom.: 1034 Cov.: 31 AF XY: 0.110 AC XY: 8148 AN XY: 74394

Gnomad4 AFR AF: 0.0595

Gnomad4 AMR AF: 0.0583

Gnomad4 ASJ AF: 0.0817

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.0780

Alfa AF: 0.116 Hom.: 585

Bravo AF: 0.0942

Asia WGS AF: 0.151 AC: 525 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	20
DANN	Benign	0.83

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

Other links and lift over

dbSNP: rs7804898; hg19: chr7-94056099;