17-82571738-G-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_004514.4(FOXK2):c.777G>T(p.Pro259=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00641 in 1,555,482 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0050 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0066 (42 hom.)
• Consequence: FOXK2 NM_004514.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.181

Genes affected

FOXK2 (HGNC:6036): (forkhead box K2) The protein encoded by this gene contains a fork head DNA binding domain. This protein can bind to the purine-rich motifs of the HIV long terminal repeat (LTR), and to the similar purine-rich motif in the interleukin 2 (IL2) promoter. It may be involved in the regulation of viral and cellular promoter elements. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 17-82571738-G-T is Benign according to our data. Variant chr17-82571738-G-T is described in ClinVar as [Benign]. Clinvar id is 717485.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.181 with no splicing effect.
• BS2: High AC in GnomAd at 763 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXK2	NM_004514.4	c.777G>T	p.Pro259=	synonymous_variant	4/9	ENST00000335255.10
FOXK2	XM_047435919.1	c.777G>T	p.Pro259=	synonymous_variant	4/9
FOXK2	XM_047435920.1	c.777G>T	p.Pro259=	synonymous_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXK2	ENST00000335255.10	c.777G>T	p.Pro259=	synonymous_variant	4/9	1	NM_004514.4	P1

Frequencies

GnomAD3 genomes AF: 0.00502 AC: 763 AN: 152124 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.00852

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.00189

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00681

Gnomad OTH AF: 0.00863

GnomAD3 exomes AF: 0.00484 AC: 980 AN: 202498 Hom.: 0 AF XY: 0.00520 AC XY: 576 AN XY: 110868

Gnomad AFR exome AF: 0.000807

Gnomad AMR exome AF: 0.00359

Gnomad ASJ exome AF: 0.00919

Gnomad EAS exome AF: 0.000148

Gnomad SAS exome AF: 0.00551

Gnomad FIN exome AF: 0.00243

Gnomad NFE exome AF: 0.00634

Gnomad OTH exome AF: 0.00459

GnomAD4 exome AF: 0.00657 AC: 9218 AN: 1403240 Hom.: 42 Cov.: 30 AF XY: 0.00658 AC XY: 4580 AN XY: 696552

Gnomad4 AFR exome AF: 0.000873

Gnomad4 AMR exome AF: 0.00453

Gnomad4 ASJ exome AF: 0.0101

Gnomad4 EAS exome AF: 0.0000555

Gnomad4 SAS exome AF: 0.00491

Gnomad4 FIN exome AF: 0.00235

Gnomad4 NFE exome AF: 0.00722

Gnomad4 OTH exome AF: 0.00753

GnomAD4 genome AF: 0.00499 AC: 760 AN: 152242 Hom.: 5 Cov.: 32 AF XY: 0.00515 AC XY: 383 AN XY: 74438

Gnomad4 AFR AF: 0.00101

Gnomad4 AMR AF: 0.00844

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00353

Gnomad4 FIN AF: 0.00189

Gnomad4 NFE AF: 0.00679

Gnomad4 OTH AF: 0.00854

Alfa AF: 0.00430 Hom.: 2

Bravo AF: 0.00560

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	2.3
Dann	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs117692271; hg19: chr17-80529614;