17-82571807-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_004514.4(FOXK2):c.846C>T(p.Asn282=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000396 in 1,603,672 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00039 (4 hom.)
• Consequence: FOXK2 NM_004514.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0750

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 17-82571807-C-T is Benign according to our data. Variant chr17-82571807-C-T is described in ClinVar as [Benign]. Clinvar id is 730235.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.075 with no splicing effect.
• BS2: High AC in GnomAd at 63 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXK2	NM_004514.4	c.846C>T	p.Asn282=	synonymous_variant	4/9	ENST00000335255.10
FOXK2	XM_047435919.1	c.846C>T	p.Asn282=	synonymous_variant	4/9
FOXK2	XM_047435920.1	c.846C>T	p.Asn282=	synonymous_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXK2	ENST00000335255.10	c.846C>T	p.Asn282=	synonymous_variant	4/9	1	NM_004514.4	P1

Frequencies

GnomAD3 genomes AF: 0.000414 AC: 63 AN: 152112 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00943

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.000480

GnomAD3 exomes AF: 0.00122 AC: 294 AN: 240552 Hom.: 2 AF XY: 0.00116 AC XY: 152 AN XY: 130530

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00151

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0131

Gnomad SAS exome AF: 0.000345

Gnomad FIN exome AF: 0.0000465

Gnomad NFE exome AF: 0.0000996

Gnomad OTH exome AF: 0.000518

GnomAD4 exome AF: 0.000394 AC: 572 AN: 1451442 Hom.: 4 Cov.: 30 AF XY: 0.000397 AC XY: 287 AN XY: 722176

Gnomad4 AFR exome AF: 0.0000307

Gnomad4 AMR exome AF: 0.00126

Gnomad4 ASJ exome AF: 0.0000385

Gnomad4 EAS exome AF: 0.0105

Gnomad4 SAS exome AF: 0.000378

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.0000496

Gnomad4 OTH exome AF: 0.000400

GnomAD4 genome AF: 0.000414 AC: 63 AN: 152230 Hom.: 0 Cov.: 32 AF XY: 0.000430 AC XY: 32 AN XY: 74438

Gnomad4 AFR AF: 0.0000482

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00945

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0000944

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.000475

Alfa AF: 0.000179 Hom.: 0

Bravo AF: 0.000623

Asia WGS AF: 0.00462 AC: 16 AN: 3478

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

Aug 15, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	8.6
Dann	Benign	0.88

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: rs187154573; hg19: chr17-80529683;