2-215361861-GT-G

Position:

• chr2-215361861-GT-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_212482.4(FN1):​c.7362+107delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0259 in 1,084,532 control chromosomes in the GnomAD database, including 98 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (15 hom., cov: 32)
  • Exomes 𝑓: 0.027 (83 hom.)
• Consequence: FN1 NM_212482.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.478

Genes affected

FN1 (HGNC:3778): (fibronectin 1) This gene encodes fibronectin, a glycoprotein present in a soluble dimeric form in plasma, and in a dimeric or multimeric form at the cell surface and in extracellular matrix. The encoded preproprotein is proteolytically processed to generate the mature protein. Fibronectin is involved in cell adhesion and migration processes including embryogenesis, wound healing, blood coagulation, host defense, and metastasis. The gene has three regions subject to alternative splicing, with the potential to produce 20 different transcript variants, at least one of which encodes an isoform that undergoes proteolytic processing. The full-length nature of some variants has not been determined. [provided by RefSeq, Jan 2016]

ATIC (HGNC:794): (5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase) This gene encodes a bifunctional protein that catalyzes the last two steps of the de novo purine biosynthetic pathway. The N-terminal domain has phosphoribosylaminoimidazolecarboxamide formyltransferase activity, and the C-terminal domain has IMP cyclohydrolase activity. A mutation in this gene results in AICA-ribosiduria. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-215361861-GT-G is Benign according to our data. Variant chr2-215361861-GT-G is described in ClinVar as [Likely_benign]. Clinvar id is 1191483.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0159 (2341/146804) while in subpopulation AFR AF= 0.0242 (971/40206). AF 95% confidence interval is 0.0229. There are 15 homozygotes in gnomad4. There are 1168 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2341 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FN1	NM_212482.4	c.7362+107delA		intron_variant		ENST00000354785.11	NP_997647.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FN1	ENST00000354785.11	c.7362+107delA		intron_variant		1	NM_212482.4	ENSP00000346839.4

Frequencies

GnomAD3 genomes AF: 0.0159 AC: 2340 AN: 146720 Hom.: 16 Cov.: 32

Gnomad AFR AF: 0.0242

Gnomad AMI AF: 0.0484

Gnomad AMR AF: 0.0156

Gnomad ASJ AF: 0.0233

Gnomad EAS AF: 0.000792

Gnomad SAS AF: 0.0131

Gnomad FIN AF: 0.00899

Gnomad MID AF: 0.0192

Gnomad NFE AF: 0.0124

Gnomad OTH AF: 0.0228

GnomAD4 exome AF: 0.0274 AC: 25716 AN: 937728 Hom.: 83 Cov.: 18 AF XY: 0.0276 AC XY: 12743 AN XY: 462262

Gnomad4 AFR exome AF: 0.0403

Gnomad4 AMR exome AF: 0.0294

Gnomad4 ASJ exome AF: 0.0451

Gnomad4 EAS exome AF: 0.0123

Gnomad4 SAS exome AF: 0.0254

Gnomad4 FIN exome AF: 0.0266

Gnomad4 NFE exome AF: 0.0271

Gnomad4 OTH exome AF: 0.0303

GnomAD4 genome AF: 0.0159 AC: 2341 AN: 146804 Hom.: 15 Cov.: 32 AF XY: 0.0163 AC XY: 1168 AN XY: 71518

Gnomad4 AFR AF: 0.0242

Gnomad4 AMR AF: 0.0156

Gnomad4 ASJ AF: 0.0233

Gnomad4 EAS AF: 0.000794

Gnomad4 SAS AF: 0.0129

Gnomad4 FIN AF: 0.00899

Gnomad4 NFE AF: 0.0124

Gnomad4 OTH AF: 0.0226

Bravo AF: 0.0166

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 18, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs55953250; hg19: chr2-216226584;