Variant 7-74338803-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_003388.5(CLIP2):c.477C>T(p.His159=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 1,611,308 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0046 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 8 hom. )

Consequence

CLIP2
NM_003388.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.285

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 7-74338803-C-T is Benign according to our data. Variant chr7-74338803-C-T is described in ClinVar as [Benign]. Clinvar id is 790596.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.285 with no splicing effect.

BS2

High AC in GnomAd4 at 694 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CLIP2	NM_003388.5 linkuse as main transcript	c.477C>T	p.His159=	synonymous_variant	3/17	ENST00000223398.11	NP_003379.4
CLIP2	NM_032421.3 linkuse as main transcript	c.477C>T	p.His159=	synonymous_variant	3/16		NP_115797.2
CLIP2	XM_047420800.1 linkuse as main transcript	c.477C>T	p.His159=	synonymous_variant	3/13		XP_047276756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLIP2	ENST00000223398.11 linkuse as main transcript	c.477C>T	p.His159=	synonymous_variant	3/17	5	NM_003388.5	ENSP00000223398	P3	Q9UDT6-1
CLIP2	ENST00000361545.9 linkuse as main transcript	c.477C>T	p.His159=	synonymous_variant	3/16	1		ENSP00000355151	A1	Q9UDT6-2

Frequencies

GnomAD3 genomes

AF:

0.00449

AC:

684

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0130

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00353

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:

0.00109

Gnomad OTH

AF:

0.00716

GnomAD3 exomes

AF:

0.00198

AC:

486

AN:

245800

Hom.:

AF XY:

0.00150

AC XY:

201

AN XY:

133984

show subpopulations

Gnomad AFR exome

AF:

0.0134

Gnomad AMR exome

AF:

0.00349

Gnomad ASJ exome

AF:

0.000603

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000197

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00112

Gnomad OTH exome

AF:

0.00332

GnomAD4 exome

AF:

0.00132

AC:

1921

AN:

1458994

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

857

AN XY:

725938

show subpopulations

Gnomad4 AFR exome

AF:

0.0134

Gnomad4 AMR exome

AF:

0.00394

Gnomad4 ASJ exome

AF:

0.000498

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000255

Gnomad4 FIN exome

AF:

0.0000196

Gnomad4 NFE exome

AF:

0.000891

Gnomad4 OTH exome

AF:

0.00345

GnomAD4 genome

AF:

0.00456

AC:

694

AN:

152314

Hom.:

Cov.:

AF XY:

0.00447

AC XY:

333

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0132

Gnomad4 AMR

AF:

0.00353

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00109

Gnomad4 OTH

AF:

0.00709

Alfa

AF:

0.00190

Hom.:

Bravo

AF:

0.00533

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00174

EpiControl

AF:

0.00160

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 05, 2018	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2022	CLIP2: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

3.7

DANN

Benign

0.84

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