dbSNP rs151111065: CLIP2:p.Arg12His (chr7-74317581-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_003388.5(CLIP2):c.35G>A(p.Arg12His) variant causes a missense change. The variant allele was found at a frequency of 0.000314 in 1,494,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00032 ( 0 hom. )

Consequence

CLIP2
NM_003388.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 4.64

Publications

8 publications found

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]

CLIP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2663772).

BS2

High AC in GnomAd4 at 37 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003388.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLIP2	NM_003388.5	MANE Select	c.35G>A	p.Arg12His	missense	Exon 2 of 17	NP_003379.4
	CLIP2	NM_032421.3		c.35G>A	p.Arg12His	missense	Exon 2 of 16	NP_115797.2	Q9UDT6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLIP2	ENST00000223398.11	TSL:5 MANE Select	c.35G>A	p.Arg12His	missense	Exon 2 of 17	ENSP00000223398.6	Q9UDT6-1
CLIP2	ENST00000361545.9	TSL:1	c.35G>A	p.Arg12His	missense	Exon 2 of 16	ENSP00000355151.5	Q9UDT6-2
CLIP2	ENST00000884300.1		c.35G>A	p.Arg12His	missense	Exon 2 of 18	ENSP00000554359.1

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

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:

0.000412

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000201

AC:

AN:

183846

AF XY:

0.000247

show subpopulations

Gnomad AFR exome

AF:

0.000172

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000909

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000291

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000322

AC:

432

AN:

1342130

Hom.:

Cov.:

AF XY:

0.000333

AC XY:

221

AN XY:

664626

show subpopulations

African (AFR)

AF:

0.0000352

AC:

AN:

28390

American (AMR)

AF:

0.000395

AC:

AN:

30352

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22274

East Asian (EAS)

AF:

0.000149

AC:

AN:

33516

South Asian (SAS)

AF:

0.0000285

AC:

AN:

70148

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50240

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5272

European-Non Finnish (NFE)

AF:

0.000383

AC:

401

AN:

1047546

Other (OTH)

AF:

0.000202

AC:

AN:

54392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

103

129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000243

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.0000721

AC:

AN:

41598

American (AMR)

AF:

0.000327

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000412

AC:

AN:

68022

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000296

Hom.:

Bravo

AF:

0.000310

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000189

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.26

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.054

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.47

MutationAssessor

Benign

1.0

PhyloP100

4.6

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.29

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.019

Polyphen

1.0

Vest4

0.40

MVP

0.88

MPC

1.9

ClinPred

0.59

GERP RS

4.5

Varity_R

0.26

gMVP

0.40

Mutation Taster

=90/10

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over