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GeneBe

7-74338695-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_003388.5(CLIP2):c.369G>A(p.Ala123=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00182 in 1,584,332 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0054 ( 3 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 14 hom. )

Consequence

CLIP2
NM_003388.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -8.79
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 7-74338695-G-A is Benign according to our data. Variant chr7-74338695-G-A is described in ClinVar as [Benign]. Clinvar id is 790595.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-8.79 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00144 (2068/1432028) while in subpopulation AFR AF= 0.0166 (546/32946). AF 95% confidence interval is 0.0154. There are 14 homozygotes in gnomad4_exome. There are 922 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 799 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CLIP2NM_003388.5 linkuse as main transcriptc.369G>A p.Ala123= synonymous_variant 3/17 ENST00000223398.11
CLIP2NM_032421.3 linkuse as main transcriptc.369G>A p.Ala123= synonymous_variant 3/16
CLIP2XM_047420800.1 linkuse as main transcriptc.369G>A p.Ala123= synonymous_variant 3/13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CLIP2ENST00000223398.11 linkuse as main transcriptc.369G>A p.Ala123= synonymous_variant 3/175 NM_003388.5 P3Q9UDT6-1
CLIP2ENST00000361545.9 linkuse as main transcriptc.369G>A p.Ala123= synonymous_variant 3/161 A1Q9UDT6-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00525
AC:
799
AN:
152186
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0156
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00373
Gnomad ASJ
AF:
0.000576
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00115
Gnomad OTH
AF:
0.00764
GnomAD3 exomes
AF:
0.00216
AC:
439
AN:
203672
Hom.:
3
AF XY:
0.00160
AC XY:
177
AN XY:
110800
show subpopulations
Gnomad AFR exome
AF:
0.0144
Gnomad AMR exome
AF:
0.00371
Gnomad ASJ exome
AF:
0.000757
Gnomad EAS exome
AF:
0.000262
Gnomad SAS exome
AF:
0.000258
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00121
Gnomad OTH exome
AF:
0.00397
GnomAD4 exome
AF:
0.00144
AC:
2068
AN:
1432028
Hom.:
14
Cov.:
33
AF XY:
0.00130
AC XY:
922
AN XY:
710848
show subpopulations
Gnomad4 AFR exome
AF:
0.0166
Gnomad4 AMR exome
AF:
0.00419
Gnomad4 ASJ exome
AF:
0.000546
Gnomad4 EAS exome
AF:
0.000236
Gnomad4 SAS exome
AF:
0.000276
Gnomad4 FIN exome
AF:
0.0000223
Gnomad4 NFE exome
AF:
0.000899
Gnomad4 OTH exome
AF:
0.00418
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00537
AC:
818
AN:
152304
Hom.:
3
Cov.:
32
AF XY:
0.00526
AC XY:
392
AN XY:
74476
show subpopulations
Gnomad4 AFR
AF:
0.0160
Gnomad4 AMR
AF:
0.00373
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00115
Gnomad4 OTH
AF:
0.00756
Alfa
AF:
0.00112
Hom.:
0
Bravo
AF:
0.00626
Asia WGS
AF:
0.00577
AC:
20
AN:
3478

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeApr 05, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
Cadd
Benign
2.9
Dann
Benign
0.89

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: rs112969082; hg19: chr7-73753025; API