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GeneBe

20-22582234-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_021784.5(FOXA2):c.1008G>A(p.Leu336=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000112 in 1,481,178 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000088 ( 0 hom. )

Consequence

FOXA2
NM_021784.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.02
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 20-22582234-C-T is Benign according to our data. Variant chr20-22582234-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2695263.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.02 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 49 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FOXA2NM_021784.5 linkuse as main transcriptc.1008G>A p.Leu336= synonymous_variant 2/2 ENST00000419308.7
FOXA2NM_153675.3 linkuse as main transcriptc.990G>A p.Leu330= synonymous_variant 3/3
FOXA2XM_047440133.1 linkuse as main transcriptc.990G>A p.Leu330= synonymous_variant 3/3
FOXA2XM_047440134.1 linkuse as main transcriptc.900G>A p.Leu300= synonymous_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FOXA2ENST00000419308.7 linkuse as main transcriptc.1008G>A p.Leu336= synonymous_variant 2/21 NM_021784.5 P4Q9Y261-2
FOXA2ENST00000377115.4 linkuse as main transcriptc.990G>A p.Leu330= synonymous_variant 3/31 A1Q9Y261-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000322
AC:
49
AN:
152104
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00242
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.000955
GnomAD3 exomes
AF:
0.000144
AC:
12
AN:
83124
Hom.:
0
AF XY:
0.000179
AC XY:
8
AN XY:
44636
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000384
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000997
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000122
Gnomad OTH exome
AF:
0.000826
GnomAD4 exome
AF:
0.0000880
AC:
117
AN:
1329074
Hom.:
0
Cov.:
35
AF XY:
0.0000721
AC XY:
47
AN XY:
652108
show subpopulations
Gnomad4 AFR exome
AF:
0.0000723
Gnomad4 AMR exome
AF:
0.000602
Gnomad4 ASJ exome
AF:
0.0000498
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000447
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000674
Gnomad4 OTH exome
AF:
0.000328
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000322
AC:
49
AN:
152104
Hom.:
0
Cov.:
33
AF XY:
0.000336
AC XY:
25
AN XY:
74296
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.00242
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.000955
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.000521

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeNov 25, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.67
Cadd
Benign
8.1
Dann
Benign
0.77
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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.

Other links and lift over

dbSNP: rs558508968; hg19: chr20-22562872; COSMIC: COSV65795642; COSMIC: COSV65795642; API