Variant 20-22582036-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_021784.5(FOXA2):c.1206A>G(p.Gln402=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.877 in 1,613,626 control chromosomes in the GnomAD database, including 621,472 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.91 ( 62772 hom., cov: 32)

Exomes 𝑓: 0.87 ( 558700 hom. )

Consequence

FOXA2
NM_021784.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0760

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 20-22582036-T-C is Benign according to our data. Variant chr20-22582036-T-C is described in ClinVar as [Benign]. Clinvar id is 1300560.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.076 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FOXA2	NM_021784.5 linkuse as main transcript	c.1206A>G	p.Gln402=	synonymous_variant	2/2	ENST00000419308.7	NP_068556.2
FOXA2	NM_153675.3 linkuse as main transcript	c.1188A>G	p.Gln396=	synonymous_variant	3/3		NP_710141.1
FOXA2	XM_047440133.1 linkuse as main transcript	c.1188A>G	p.Gln396=	synonymous_variant	3/3		XP_047296089.1
FOXA2	XM_047440134.1 linkuse as main transcript	c.1098A>G	p.Gln366=	synonymous_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.1206A>G	p.Gln402=	synonymous_variant	2/2	1	NM_021784.5	ENSP00000400341	P4	Q9Y261-2
FOXA2	ENST00000377115.4 linkuse as main transcript	c.1188A>G	p.Gln396=	synonymous_variant	3/3	1		ENSP00000366319	A1	Q9Y261-1

Frequencies

GnomAD3 genomes

AF:

0.907

AC:

137923

AN:

152074

Hom.:

62712

Cov.:

show subpopulations

Gnomad AFR

AF:

0.975

Gnomad AMI

AF:

0.905

Gnomad AMR

AF:

0.908

Gnomad ASJ

AF:

0.887

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.967

Gnomad FIN

AF:

0.879

Gnomad MID

AF:

0.848

Gnomad NFE

AF:

0.860

Gnomad OTH

AF:

0.894

GnomAD3 exomes

AF:

0.901

AC:

225247

AN:

249896

Hom.:

101863

AF XY:

0.900

AC XY:

121607

AN XY:

135094

show subpopulations

Gnomad AFR exome

AF:

0.976

Gnomad AMR exome

AF:

0.937

Gnomad ASJ exome

AF:

0.887

Gnomad EAS exome

AF:

0.999

Gnomad SAS exome

AF:

0.956

Gnomad FIN exome

AF:

0.872

Gnomad NFE exome

AF:

0.857

Gnomad OTH exome

AF:

0.878

GnomAD4 exome

AF:

0.873

AC:

1276442

AN:

1461434

Hom.:

558700

Cov.:

AF XY:

0.876

AC XY:

636719

AN XY:

727024

show subpopulations

Gnomad4 AFR exome

AF:

0.977

Gnomad4 AMR exome

AF:

0.936

Gnomad4 ASJ exome

AF:

0.888

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.957

Gnomad4 FIN exome

AF:

0.872

Gnomad4 NFE exome

AF:

0.856

Gnomad4 OTH exome

AF:

0.884

GnomAD4 genome

AF:

0.907

AC:

138042

AN:

152192

Hom.:

62772

Cov.:

AF XY:

0.910

AC XY:

67654

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.975

Gnomad4 AMR

AF:

0.909

Gnomad4 ASJ

AF:

0.887

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.966

Gnomad4 FIN

AF:

0.879

Gnomad4 NFE

AF:

0.860

Gnomad4 OTH

AF:

0.895

Alfa

AF:

0.874

Hom.:

81838

Bravo

AF:

0.912

Asia WGS

AF:

0.980

AC:

3408

AN:

3478

EpiCase

AF:

0.859

EpiControl

AF:

0.858

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.5

DANN

Benign

0.47

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