2-232735194-A-C

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001103146.3(GIGYF2):​c.-4A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 1,591,010 control chromosomes in the GnomAD database, including 105,819 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 7997 hom., cov: 32)
Exomes 𝑓: 0.36 ( 97822 hom. )

Consequence

GIGYF2
NM_001103146.3 5_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.72
Variant links:
Genes affected
GIGYF2 (HGNC:11960): (GRB10 interacting GYF protein 2) This gene contains CAG trinucleotide repeats and encodes a protein containing several stretches of polyglutamine residues. The encoded protein may be involved in the regulation of tyrosine kinase receptor signaling. This gene is located in a chromosomal region that was genetically linked to Parkinson disease type 11, and mutations in this gene were thought to be causative for this disease. However, more recent studies in different populations have been unable to replicate this association. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.23).
BP6
Variant 2-232735194-A-C is Benign according to our data. Variant chr2-232735194-A-C is described in ClinVar as [Benign]. Clinvar id is 1246966.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-232735194-A-C is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GIGYF2NM_001103146.3 linkuse as main transcriptc.-4A>C 5_prime_UTR_variant 3/29 ENST00000373563.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GIGYF2ENST00000373563.9 linkuse as main transcriptc.-4A>C 5_prime_UTR_variant 3/291 NM_001103146.3 P4Q6Y7W6-1

Frequencies

GnomAD3 genomes
AF:
0.317
AC:
48158
AN:
152008
Hom.:
7988
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.267
Gnomad AMI
AF:
0.365
Gnomad AMR
AF:
0.291
Gnomad ASJ
AF:
0.337
Gnomad EAS
AF:
0.333
Gnomad SAS
AF:
0.623
Gnomad FIN
AF:
0.237
Gnomad MID
AF:
0.366
Gnomad NFE
AF:
0.341
Gnomad OTH
AF:
0.310
GnomAD3 exomes
AF:
0.349
AC:
87432
AN:
250634
Hom.:
16996
AF XY:
0.367
AC XY:
49758
AN XY:
135454
show subpopulations
Gnomad AFR exome
AF:
0.264
Gnomad AMR exome
AF:
0.251
Gnomad ASJ exome
AF:
0.337
Gnomad EAS exome
AF:
0.326
Gnomad SAS exome
AF:
0.638
Gnomad FIN exome
AF:
0.238
Gnomad NFE exome
AF:
0.339
Gnomad OTH exome
AF:
0.344
GnomAD4 exome
AF:
0.358
AC:
515414
AN:
1438884
Hom.:
97822
Cov.:
27
AF XY:
0.367
AC XY:
263075
AN XY:
717100
show subpopulations
Gnomad4 AFR exome
AF:
0.267
Gnomad4 AMR exome
AF:
0.256
Gnomad4 ASJ exome
AF:
0.331
Gnomad4 EAS exome
AF:
0.291
Gnomad4 SAS exome
AF:
0.628
Gnomad4 FIN exome
AF:
0.239
Gnomad4 NFE exome
AF:
0.352
Gnomad4 OTH exome
AF:
0.362
GnomAD4 genome
AF:
0.317
AC:
48182
AN:
152126
Hom.:
7997
Cov.:
32
AF XY:
0.316
AC XY:
23515
AN XY:
74386
show subpopulations
Gnomad4 AFR
AF:
0.266
Gnomad4 AMR
AF:
0.291
Gnomad4 ASJ
AF:
0.337
Gnomad4 EAS
AF:
0.333
Gnomad4 SAS
AF:
0.623
Gnomad4 FIN
AF:
0.237
Gnomad4 NFE
AF:
0.341
Gnomad4 OTH
AF:
0.318
Alfa
AF:
0.332
Hom.:
11371
Bravo
AF:
0.309
Asia WGS
AF:
0.494
AC:
1716
AN:
3478
EpiCase
AF:
0.347
EpiControl
AF:
0.344

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxFeb 22, 2020- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.23
CADD
Benign
16
DANN
Benign
0.93
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs11555646; hg19: chr2-233599904; COSMIC: COSV65247676; COSMIC: COSV65247676; API