Variant chr20-22582217-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_021784.5(FOXA2):c.1025C>T(p.Ala342Val) variant causes a missense change. The variant allele was found at a frequency of 0.000122 in 1,539,270 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

FOXA2
NM_021784.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.69

Variant links:

Genes affected

FOXA2 (HGNC:5022): (forkhead box A2) This gene encodes a member of the forkhead class of DNA-binding proteins. These hepatocyte nuclear factors are transcriptional activators for liver-specific genes such as albumin and transthyretin, and they also interact with chromatin. Similar family members in mice have roles in the regulation of metabolism and in the differentiation of the pancreas and liver. This gene has been linked to sporadic cases of maturity-onset diabetes of the young. Transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Oct 2008]

FOXA2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.031162411).

BP6

Variant 20-22582217-G-A is Benign according to our data. Variant chr20-22582217-G-A is described in ClinVar as [Benign]. Clinvar id is 2960229.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 35 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FOXA2	NM_021784.5 linkuse as main transcript	c.1025C>T	p.Ala342Val	missense_variant	2/2	ENST00000419308.7	NP_068556.2
FOXA2	NM_153675.3 linkuse as main transcript	c.1007C>T	p.Ala336Val	missense_variant	3/3		NP_710141.1
FOXA2	XM_047440133.1 linkuse as main transcript	c.1007C>T	p.Ala336Val	missense_variant	3/3		XP_047296089.1
FOXA2	XM_047440134.1 linkuse as main transcript	c.917C>T	p.Ala306Val	missense_variant	2/2		XP_047296090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXA2	ENST00000419308.7 linkuse as main transcript	c.1025C>T	p.Ala342Val	missense_variant	2/2	1	NM_021784.5	ENSP00000400341	P4	Q9Y261-2
FOXA2	ENST00000377115.4 linkuse as main transcript	c.1007C>T	p.Ala336Val	missense_variant	3/3	1		ENSP00000366319	A1	Q9Y261-1

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00320

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000451

AC:

AN:

137512

Hom.:

AF XY:

0.000381

AC XY:

AN XY:

73444

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00428

Gnomad NFE exome

AF:

0.0000200

Gnomad OTH exome

AF:

0.000252

GnomAD4 exome

AF:

0.000110

AC:

153

AN:

1387128

Hom.:

Cov.:

AF XY:

0.000101

AC XY:

AN XY:

683138

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00304

Gnomad4 NFE exome

AF:

0.00000466

Gnomad4 OTH exome

AF:

0.0000697

GnomAD4 genome

AF:

0.000230

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00320

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000660

Hom.:

ExAC

AF:

0.0000852

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 27, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.016

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.34

.;T

Eigen

Benign

0.010

Eigen_PC

Benign

0.061

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.68

T;T

M_CAP

Pathogenic

0.60

MetaRNN

Benign

0.031

T;T

MetaSVM

Uncertain

-0.027

MutationAssessor

Benign

1.1

.;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.31

.;N

REVEL

Uncertain

0.33

Sift

Benign

0.22

.;T

Sift4G

Benign

0.47

T;T

Polyphen

0.67

.;P

Vest4

0.24

MVP

0.81

ClinPred

0.076

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.44

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over