7-94426732-G-T

Position:

• chr7-94426732-G-T

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.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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
COL1A2	NM_000089.4	c.3105+202G>T		intron_variant		ENST00000297268.11	NP_000080.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL1A2	ENST00000297268.11	c.3105+202G>T		intron_variant		1	NM_000089.4	ENSP00000297268.6
COL1A2	ENST00000481570.5	n.3280G>T		non_coding_transcript_exon_variant	5/8	2
COL1A2	ENST00000488121.1	n.21+202G>T		intron_variant		2
COL1A2	ENST00000478215.1	n.*3G>T		downstream_gene_variant		3

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

Gnomad4 AFR exome AF: 0.709

Gnomad4 AMR exome AF: 0.825

Gnomad4 ASJ exome AF: 0.713

Gnomad4 EAS exome AF: 0.932

Gnomad4 SAS exome AF: 0.656

Gnomad4 FIN exome AF: 0.787

Gnomad4 NFE exome AF: 0.766

Gnomad4 OTH exome AF: 0.749

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

Gnomad4 AFR AF: 0.715

Gnomad4 AMR AF: 0.798

Gnomad4 ASJ AF: 0.710

Gnomad4 EAS AF: 0.907

Gnomad4 SAS AF: 0.669

Gnomad4 FIN AF: 0.792

Gnomad4 NFE AF: 0.767

Gnomad4 OTH AF: 0.732

Alfa AF: 0.763 Hom.: 42025

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -
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	7.5
DANN	Benign	0.56

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: rs2621215; hg19: chr7-94056044;