chr7-74317586-G-A

Variant summary

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

The NM_003388.5(CLIP2):​c.40G>A​(p.Gly14Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000223 in 1,348,096 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

CLIP2
NM_003388.5 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.64
Variant links:
Genes affected
CLIP2 (HGNC:2586): (CAP-Gly domain containing linker protein 2) The protein encoded by this gene belongs to the family of cytoplasmic linker proteins, which have been proposed to mediate the interaction between specific membranous organelles and microtubules. This protein was found to associate with both microtubules and an organelle called the dendritic lamellar body. This gene is hemizygously deleted in Williams syndrome, a multisystem developmental disorder caused by the deletion of contiguous genes at 7q11.23. Alternative splicing of this gene generates 2 transcript variants. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CLIP2NM_003388.5 linkuse as main transcriptc.40G>A p.Gly14Arg missense_variant 2/17 ENST00000223398.11
CLIP2NM_032421.3 linkuse as main transcriptc.40G>A p.Gly14Arg missense_variant 2/16
CLIP2XM_047420800.1 linkuse as main transcriptc.40G>A p.Gly14Arg missense_variant 2/13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CLIP2ENST00000223398.11 linkuse as main transcriptc.40G>A p.Gly14Arg missense_variant 2/175 NM_003388.5 P3Q9UDT6-1
CLIP2ENST00000361545.9 linkuse as main transcriptc.40G>A p.Gly14Arg missense_variant 2/161 A1Q9UDT6-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000223
AC:
3
AN:
1348096
Hom.:
0
Cov.:
30
AF XY:
0.00000150
AC XY:
1
AN XY:
667940
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
0.00000286
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 30, 2023The c.40G>A (p.G14R) alteration is located in exon 2 (coding exon 1) of the CLIP2 gene. This alteration results from a G to A substitution at nucleotide position 40, causing the glycine (G) at amino acid position 14 to be replaced by an arginine (R). 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
Uncertain
0.49
BayesDel_addAF
Benign
0.0072
T
BayesDel_noAF
Benign
-0.23
CADD
Uncertain
24
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.094
.;T;T
Eigen
Uncertain
0.41
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Uncertain
0.95
D;D;.
M_CAP
Benign
0.043
D
MetaRNN
Uncertain
0.59
D;D;D
MetaSVM
Benign
-0.45
T
MutationAssessor
Benign
0.90
L;L;L
MutationTaster
Benign
0.70
D;D;D
PrimateAI
Uncertain
0.73
T
PROVEAN
Benign
-2.1
N;N;N
REVEL
Benign
0.22
Sift
Benign
0.11
T;T;T
Sift4G
Benign
0.53
T;T;T
Polyphen
0.99
D;D;D
Vest4
0.75
MutPred
0.29
Gain of methylation at G14 (P = 0.0042);Gain of methylation at G14 (P = 0.0042);Gain of methylation at G14 (P = 0.0042);
MVP
0.78
MPC
1.7
ClinPred
0.84
D
GERP RS
4.5
Varity_R
0.18
gMVP
0.32

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-73731916; COSMIC: COSV56279845; API