3-51863107-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_203424.2(IQCF2):​c.232C>T​(p.Arg78Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00018 in 1,614,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 30)
Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

IQCF2
NM_203424.2 missense

Scores

5
6
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.459
Variant links:
Genes affected
IQCF2 (HGNC:31815): (IQ motif containing F2) Predicted to enable calmodulin binding activity. [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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.886

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IQCF2NM_203424.2 linkc.232C>T p.Arg78Trp missense_variant Exon 3 of 3 ENST00000333127.4 NP_982248.1 Q8IXL9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IQCF2ENST00000333127.4 linkc.232C>T p.Arg78Trp missense_variant Exon 3 of 3 1 NM_203424.2 ENSP00000329904.3 Q8IXL9
IQCF2ENST00000429548.1 linkn.311C>T non_coding_transcript_exon_variant Exon 3 of 3 2

Frequencies

GnomAD3 genomes
AF:
0.000118
AC:
18
AN:
152214
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.000220
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000111
AC:
28
AN:
251374
Hom.:
0
AF XY:
0.0000589
AC XY:
8
AN XY:
135868
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.0000992
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000194
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000187
AC:
273
AN:
1461886
Hom.:
0
Cov.:
32
AF XY:
0.000173
AC XY:
126
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.0000765
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000230
Gnomad4 OTH exome
AF:
0.000132
GnomAD4 genome
AF:
0.000118
AC:
18
AN:
152214
Hom.:
0
Cov.:
30
AF XY:
0.000148
AC XY:
11
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000220
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000176
Hom.:
0
Bravo
AF:
0.000140
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000906
AC:
11
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jun 11, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.232C>T (p.R78W) alteration is located in exon 3 (coding exon 3) of the IQCF2 gene. This alteration results from a C to T substitution at nucleotide position 232, causing the arginine (R) at amino acid position 78 to be replaced by a tryptophan (W). 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
0.27
BayesDel_addAF
Uncertain
0.023
T
BayesDel_noAF
Uncertain
0.070
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.24
T
Eigen
Benign
-0.48
Eigen_PC
Benign
-0.79
FATHMM_MKL
Benign
0.22
N
LIST_S2
Uncertain
0.89
D
M_CAP
Benign
0.082
D
MetaRNN
Pathogenic
0.89
D
MetaSVM
Uncertain
0.28
D
MutationAssessor
Pathogenic
3.2
M
PrimateAI
Benign
0.48
T
PROVEAN
Pathogenic
-6.9
D
REVEL
Uncertain
0.54
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.70
MVP
0.34
MPC
0.99
ClinPred
0.46
T
GERP RS
-9.8
Varity_R
0.49
gMVP
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.

Other links and lift over

dbSNP: rs368553100; hg19: chr3-51897123; COSMIC: COSV60761071; API