Variant chr7-74338861-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_003388.5(CLIP2):c.535C>T(p.Pro179Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00413 in 1,608,964 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0032 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0042 ( 47 hom. )

Consequence

CLIP2
NM_003388.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.70

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 made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0058303773).

BP6

Variant 7-74338861-C-T is Benign according to our data. Variant chr7-74338861-C-T is described in ClinVar as [Benign]. Clinvar id is 771871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 484 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CLIP2	NM_003388.5 linkuse as main transcript	c.535C>T	p.Pro179Ser	missense_variant	3/17	ENST00000223398.11
CLIP2	NM_032421.3 linkuse as main transcript	c.535C>T	p.Pro179Ser	missense_variant	3/16
CLIP2	XM_047420800.1 linkuse as main transcript	c.535C>T	p.Pro179Ser	missense_variant	3/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLIP2	ENST00000223398.11 linkuse as main transcript	c.535C>T	p.Pro179Ser	missense_variant	3/17	5	NM_003388.5	P3	Q9UDT6-1
CLIP2	ENST00000361545.9 linkuse as main transcript	c.535C>T	p.Pro179Ser	missense_variant	3/16	1		A1	Q9UDT6-2

Frequencies

GnomAD3 genomes

AF:

0.00317

AC:

483

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000988

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0110

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00450

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00435

AC:

1053

AN:

241994

Hom.:

AF XY:

0.00491

AC XY:

651

AN XY:

132622

show subpopulations

Gnomad AFR exome

AF:

0.000854

Gnomad AMR exome

AF:

0.00293

Gnomad ASJ exome

AF:

0.00423

Gnomad EAS exome

AF:

0.000388

Gnomad SAS exome

AF:

0.0105

Gnomad FIN exome

AF:

0.000222

Gnomad NFE exome

AF:

0.00494

Gnomad OTH exome

AF:

0.00399

GnomAD4 exome

AF:

0.00423

AC:

6163

AN:

1456602

Hom.:

Cov.:

AF XY:

0.00458

AC XY:

3317

AN XY:

724888

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.00322

Gnomad4 ASJ exome

AF:

0.00437

Gnomad4 EAS exome

AF:

0.000454

Gnomad4 SAS exome

AF:

0.0102

Gnomad4 FIN exome

AF:

0.000352

Gnomad4 NFE exome

AF:

0.00414

Gnomad4 OTH exome

AF:

0.00495

GnomAD4 genome

AF:

0.00318

AC:

484

AN:

152362

Hom.:

Cov.:

AF XY:

0.00313

AC XY:

233

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.000986

Gnomad4 AMR

AF:

0.00300

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0116

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00450

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00480

Hom.:

Bravo

AF:

0.00317

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.00230

AC:

ESP6500EA

AF:

0.00363

AC:

ExAC

AF:

0.00440

AC:

531

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.00654

EpiControl

AF:

0.00741

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 submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2023	CLIP2: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Mar 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.095

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.80

T;T;.

MetaRNN

Benign

0.0058

T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.69

N;N;N

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.7

N;N;N

REVEL

Benign

0.14

Sift

Benign

0.070

T;T;T

Sift4G

Uncertain

0.055

T;D;D

Polyphen

0.0070

B;B;B

Vest4

0.34

MVP

0.43

MPC

0.76

ClinPred

0.023

GERP RS

4.9

Varity_R

0.067

gMVP

0.60

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over