chr7-74338537-G-C
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_003388.5(CLIP2):c.211G>C(p.Val71Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000324 in 1,602,640 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000034 ( 1 hom. )
Consequence
CLIP2
NM_003388.5 missense
NM_003388.5 missense
Scores
1
5
12
Clinical Significance
Conservation
PhyloP100: 9.16
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.062494874).
BS2
?
High AC in GnomAdExome at 22 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLIP2 | NM_003388.5 | c.211G>C | p.Val71Leu | missense_variant | 3/17 | ENST00000223398.11 | |
CLIP2 | NM_032421.3 | c.211G>C | p.Val71Leu | missense_variant | 3/16 | ||
CLIP2 | XM_047420800.1 | c.211G>C | p.Val71Leu | missense_variant | 3/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLIP2 | ENST00000223398.11 | c.211G>C | p.Val71Leu | missense_variant | 3/17 | 5 | NM_003388.5 | P3 | |
CLIP2 | ENST00000361545.9 | c.211G>C | p.Val71Leu | missense_variant | 3/16 | 1 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152186Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000976 AC: 22AN: 225338Hom.: 0 AF XY: 0.000147 AC XY: 18AN XY: 122638
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GnomAD4 exome AF: 0.0000345 AC: 50AN: 1450336Hom.: 1 Cov.: 33 AF XY: 0.0000527 AC XY: 38AN XY: 721006
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152304Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74472
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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 submitter | clinical testing | Ambry Genetics | Jan 17, 2024 | The c.211G>C (p.V71L) alteration is located in exon 3 (coding exon 2) of the CLIP2 gene. This alteration results from a G to C substitution at nucleotide position 211, causing the valine (V) at amino acid position 71 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;.
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
P;P;P
Vest4
MutPred
Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);
MVP
MPC
1.4
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at