NM_021784.5:c.*177C>G

Variant names:

• chr20-22581673-G-C
• rs1974
• NM_021784.5:c.*177C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021784.5(FOXA2):​c.*177C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FOXA2 NM_021784.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.949
• Publications: 7 publications found

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 Gene-Disease associations (from GenCC):

• combined pituitary hormone deficiencies, genetic form

  Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021784.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXA2	NM_021784.5	MANE Select	c.*177C>G		3_prime_UTR	Exon 2 of 2	NP_068556.2	B0ZTD4
	FOXA2	NM_153675.3		c.*177C>G		3_prime_UTR	Exon 3 of 3	NP_710141.1	Q9Y261-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXA2	ENST00000419308.7	TSL:1 MANE Select	c.*177C>G		3_prime_UTR	Exon 2 of 2	ENSP00000400341.3	Q9Y261-2
	FOXA2	ENST00000377115.4	TSL:1	c.*177C>G		3_prime_UTR	Exon 3 of 3	ENSP00000366319.4	Q9Y261-1
	FOXA2	ENST00000938926.1		c.*177C>G		3_prime_UTR	Exon 2 of 2	ENSP00000608985.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 455762 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 238404

African (AFR) AF: 0.00 AC: 0 AN: 12580

American (AMR) AF: 0.00 AC: 0 AN: 18886

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13416

East Asian (EAS) AF: 0.00 AC: 0 AN: 31030

South Asian (SAS) AF: 0.00 AC: 0 AN: 42516

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35150

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1922

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 274222

Other (OTH) AF: 0.00 AC: 0 AN: 26040

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 2628

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.2
DANN	Benign	0.67
PhyloP100		0.95

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

Other links and lift over

dbSNP: rs1974; hg19: chr20-22562311;