Variant 7-74338695-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

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

Clinical Significance

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

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]

CLIP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

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_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-8.79 with no splicing effect.

BS1

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

High AC in GnomAd4 at 818 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CLIP2	NM_003388.5 linkuse as main transcript	c.369G>A	p.Ala123=	synonymous_variant	3/17	ENST00000223398.11
CLIP2	NM_032421.3 linkuse as main transcript	c.369G>A	p.Ala123=	synonymous_variant	3/16
CLIP2	XM_047420800.1 linkuse as main transcript	c.369G>A	p.Ala123=	synonymous_variant	3/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLIP2	ENST00000223398.11 linkuse as main transcript	c.369G>A	p.Ala123=	synonymous_variant	3/17	5	NM_003388.5	P3	Q9UDT6-1
CLIP2	ENST00000361545.9 linkuse as main transcript	c.369G>A	p.Ala123=	synonymous_variant	3/16	1		A1	Q9UDT6-2

Frequencies

GnomAD3 genomes

AF:

0.00525

AC:

799

AN:

152186

Hom.:

Cov.:

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.:

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.:

Cov.:

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

AF:

0.00537

AC:

818

AN:

152304

Hom.:

Cov.:

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.:

Bravo

AF:

0.00626

Asia WGS

AF:

0.00577

AC:

AN:

3478

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 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.

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