2-215361861-G-GTT

Position:

• chr2-215361861-G-GTT

Variant summary

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

The ENST00000354785.11(FN1):​c.7362+106_7362+107dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,131,334 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0053 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00063 (0 hom.)
• Consequence: FN1 ENST00000354785.11 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]

FN1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-215361861-G-GTT is Benign according to our data. Variant chr2-215361861-G-GTT is described in ClinVar as [Likely_benign]. Clinvar id is 1201817.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00529 (777/146888) while in subpopulation AFR AF= 0.0184 (738/40210). AF 95% confidence interval is 0.0173. There are 6 homozygotes in gnomad4. There are 372 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 777 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FN1	NM_212482.4	c.7362+106_7362+107dupAA		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+106_7362+107dupAA		intron_variant		1	NM_212482.4	ENSP00000346839.4

Frequencies

GnomAD3 genomes AF: 0.00530 AC: 778 AN: 146804 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0184

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00184

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000198

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000604

Gnomad OTH AF: 0.00347

GnomAD4 exome AF: 0.000631 AC: 621 AN: 984446 Hom.: 0 Cov.: 18 AF XY: 0.000578 AC XY: 281 AN XY: 486330

Gnomad4 AFR exome AF: 0.0188

Gnomad4 AMR exome AF: 0.00171

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000501

Gnomad4 SAS exome AF: 0.000128

Gnomad4 FIN exome AF: 0.0000296

Gnomad4 NFE exome AF: 0.000112

Gnomad4 OTH exome AF: 0.00152

GnomAD4 genome AF: 0.00529 AC: 777 AN: 146888 Hom.: 6 Cov.: 32 AF XY: 0.00520 AC XY: 372 AN XY: 71564

Gnomad4 AFR AF: 0.0184

Gnomad4 AMR AF: 0.00184

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000198

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000604

Gnomad4 OTH AF: 0.00344

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

May 01, 2020

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Computational scores

Source: dbNSFP v4.3

Splicing

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;