chr22-36506212-G-T

Position:

• chr22-36506212-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001102371.2(FOXRED2):​c.211C>A​(p.Arg71Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R71C) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FOXRED2 NM_001102371.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.81

Genes affected

FOXRED2 (HGNC:26264): (FAD dependent oxidoreductase domain containing 2) Enables flavin adenine dinucleotide binding activity. Involved in ubiquitin-dependent ERAD pathway. Located in endoplasmic reticulum lumen. [provided by Alliance of Genome Resources, Apr 2022]

FOXRED2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23123336).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXRED2	NM_001102371.2	c.211C>A	p.Arg71Ser	missense_variant	2/9	ENST00000397224.9	NP_001095841.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXRED2	ENST00000397224.9	c.211C>A	p.Arg71Ser	missense_variant	2/9	1	NM_001102371.2	ENSP00000380401.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 250060 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135404

Gnomad AFR exome AF: 0.0000617

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: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461748 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727190

Gnomad4 AFR exome AF: 0.0000597

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: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0023	T;T;T;.
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.91	.;.;D;D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.23	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;L;L;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.93	N;N;N;N
REVEL	Benign	0.096
Sift	Benign	0.52	T;T;T;T
Sift4G	Benign	0.73	T;T;T;.
Polyphen		0.63	P;P;P;.
Vest4		0.36
MutPred		0.52		Loss of MoRF binding (P = 0.0173);Loss of MoRF binding (P = 0.0173);Loss of MoRF binding (P = 0.0173);Loss of MoRF binding (P = 0.0173);
MVP		0.38
MPC		1.1
ClinPred		0.27	T
GERP RS		5.0
Varity_R		0.39
gMVP		0.79

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: rs56767103; hg19: chr22-36902259;