7-74370840-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003388.5(CLIP2):c.1381-2092G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,534 control chromosomes in the GnomAD database, including 11,241 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.37 (11241 hom., cov: 29)
• Consequence: CLIP2 NM_003388.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.958

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLIP2	NM_003388.5	c.1381-2092G>C		intron_variant		ENST00000223398.11
CLIP2	NM_032421.3	c.1381-5047G>C		intron_variant
CLIP2	XM_047420800.1	c.1381-2092G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLIP2	ENST00000223398.11	c.1381-2092G>C		intron_variant		5	NM_003388.5	P3
CLIP2	ENST00000361545.9	c.1381-5047G>C		intron_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.370 AC: 55994 AN: 151416 Hom.: 11227 Cov.: 29

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.494

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.415

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.370 AC: 56025 AN: 151534 Hom.: 11241 Cov.: 29 AF XY: 0.369 AC XY: 27312 AN XY: 74026

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.403

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.387

Gnomad4 SAS AF: 0.456

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.422

Alfa AF: 0.289 Hom.: 876

Bravo AF: 0.363

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.41
Dann	Benign	0.56

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: rs2528994; hg19: chr7-73785170;