rs11764718

Positions:

• chr7-94430005-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000089.4(COL1A2):​c.3955-242G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 549,634 control chromosomes in the GnomAD database, including 15,430 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3261 hom., cov: 32)
  • Exomes 𝑓: 0.24 (12169 hom.)
• Consequence: COL1A2 NM_000089.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.441

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 7-94430005-G-A is Benign according to our data. Variant chr7-94430005-G-A is described in ClinVar as [Benign]. Clinvar id is 1248714.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL1A2	NM_000089.4	c.3955-242G>A		intron_variant		ENST00000297268.11	NP_000080.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL1A2	ENST00000297268.11	c.3955-242G>A		intron_variant		1	NM_000089.4	ENSP00000297268.6
COL1A2	ENST00000481570.5	n.5310G>A		non_coding_transcript_exon_variant	8/8	2
COL1A2	ENST00000464916.1	n.1003-242G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28665 AN: 152050 Hom.: 3260 Cov.: 32

Gnomad AFR AF: 0.0744

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.225

GnomAD4 exome AF: 0.238 AC: 94645 AN: 397466 Hom.: 12169 Cov.: 4 AF XY: 0.246 AC XY: 52235 AN XY: 211948

Gnomad4 AFR exome AF: 0.0765

Gnomad4 AMR exome AF: 0.271

Gnomad4 ASJ exome AF: 0.261

Gnomad4 EAS exome AF: 0.149

Gnomad4 SAS exome AF: 0.362

Gnomad4 FIN exome AF: 0.141

Gnomad4 NFE exome AF: 0.238

Gnomad4 OTH exome AF: 0.235

GnomAD4 genome AF: 0.188 AC: 28663 AN: 152168 Hom.: 3261 Cov.: 32 AF XY: 0.187 AC XY: 13898 AN XY: 74394

Gnomad4 AFR AF: 0.0743

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.224

Alfa AF: 0.231 Hom.: 2208

Bravo AF: 0.190

Asia WGS AF: 0.252 AC: 876 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	clinical testing	GeneDx	Aug 18, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.28

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: rs11764718; hg19: chr7-94059317;