3-50289305-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006764.5(IFRD2):​c.835G>A​(p.Ala279Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000127 in 1,598,932 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

IFRD2
NM_006764.5 missense

Scores

1
10
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.86
Variant links:
Genes affected
IFRD2 (HGNC:5457): (interferon related developmental regulator 2) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2831809).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IFRD2NM_006764.5 linkc.835G>A p.Ala279Thr missense_variant Exon 8 of 12 ENST00000417626.8 NP_006755.5 Q12894

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IFRD2ENST00000417626.8 linkc.835G>A p.Ala279Thr missense_variant Exon 8 of 12 1 NM_006764.5 ENSP00000402849.4 Q12894

Frequencies

GnomAD3 genomes
AF:
0.000131
AC:
20
AN:
152226
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000191
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000102
AC:
23
AN:
224390
Hom.:
0
AF XY:
0.0000904
AC XY:
11
AN XY:
121670
show subpopulations
Gnomad AFR exome
AF:
0.0000773
Gnomad AMR exome
AF:
0.0000630
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:
0.000199
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000127
AC:
183
AN:
1446588
Hom.:
0
Cov.:
32
AF XY:
0.000116
AC XY:
83
AN XY:
718156
show subpopulations
Gnomad4 AFR exome
AF:
0.000151
Gnomad4 AMR exome
AF:
0.0000472
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000257
Gnomad4 SAS exome
AF:
0.0000239
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000149
Gnomad4 OTH exome
AF:
0.000134
GnomAD4 genome
AF:
0.000131
AC:
20
AN:
152344
Hom.:
0
Cov.:
33
AF XY:
0.000134
AC XY:
10
AN XY:
74508
show subpopulations
Gnomad4 AFR
AF:
0.0000962
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000191
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000327
Hom.:
0
Bravo
AF:
0.000208
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000240
AC:
2
ExAC
AF:
0.0000580
AC:
7

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 04, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1027G>A (p.A343T) alteration is located in exon 8 (coding exon 8) of the IFRD2 gene. This alteration results from a G to A substitution at nucleotide position 1027, causing the alanine (A) at amino acid position 343 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.095
BayesDel_addAF
Uncertain
0.028
T
BayesDel_noAF
Uncertain
0.080
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.24
T;T
Eigen
Uncertain
0.53
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Uncertain
0.89
D;D
M_CAP
Uncertain
0.13
D
MetaRNN
Benign
0.28
T;T
MetaSVM
Uncertain
-0.070
T
MutationAssessor
Benign
1.9
M;.
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-2.2
.;N
REVEL
Uncertain
0.45
Sift
Benign
0.069
.;T
Sift4G
Benign
0.092
T;T
Polyphen
1.0
D;.
Vest4
0.56
MVP
0.84
ClinPred
0.13
T
GERP RS
5.5
Varity_R
0.20
gMVP
0.51

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs375653258; hg19: chr3-50326736; API