7-74338803-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.285

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]

ACMG classification

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 GnomAd at 684 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLIP2	NM_003388.5	c.477C>T	p.His159=	synonymous_variant	3/17	ENST00000223398.11
CLIP2	NM_032421.3	c.477C>T	p.His159=	synonymous_variant	3/16
CLIP2	XM_047420800.1	c.477C>T	p.His159=	synonymous_variant	3/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLIP2	ENST00000223398.11	c.477C>T	p.His159=	synonymous_variant	3/17	5	NM_003388.5	P3
CLIP2	ENST00000361545.9	c.477C>T	p.His159=	synonymous_variant	3/16	1		A1

Frequencies

GnomAD3 genomes AF: 0.00449 AC: 684 AN: 152196 Hom.: 1 Cov.: 32

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.: 2 AF XY: 0.00150 AC XY: 201 AN XY: 133984

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.: 8 Cov.: 33 AF XY: 0.00118 AC XY: 857 AN XY: 725938

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.: 3 Cov.: 32 AF XY: 0.00447 AC XY: 333 AN XY: 74470

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.: 0

Bravo AF: 0.00533

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.00174

EpiControl AF: 0.00160

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2022	CLIP2: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Apr 05, 2018	- -

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

Other links and lift over

dbSNP: rs111609508; hg19: chr7-73753133;