rs229884

Variant names:

• chr7-74307921-G-A
• rs229884
• NM_003388.5:c.-67-9559G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003388.5(CLIP2):​c.-67-9559G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 152,052 control chromosomes in the GnomAD database, including 29,646 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 0.60 (29646 hom., cov: 32)
• Consequence: CLIP2 NM_003388.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.42
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003388.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLIP2	NM_003388.5	MANE Select	c.-67-9559G>A		intron	N/A	NP_003379.4
	CLIP2	NM_032421.3		c.-67-9559G>A		intron	N/A	NP_115797.2	Q9UDT6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLIP2	ENST00000223398.11	TSL:5 MANE Select	c.-67-9559G>A		intron	N/A	ENSP00000223398.6	Q9UDT6-1
	CLIP2	ENST00000361545.9	TSL:1	c.-67-9559G>A		intron	N/A	ENSP00000355151.5	Q9UDT6-2
	CLIP2	ENST00000884300.1		c.-67-9559G>A		intron	N/A	ENSP00000554359.1

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90536 AN: 151934 Hom.: 29642 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.838

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.716

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.737

Gnomad OTH AF: 0.616

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

GnomAD4 genome AF: 0.596 AC: 90558 AN: 152052 Hom.: 29646 Cov.: 32 AF XY: 0.595 AC XY: 44221 AN XY: 74326

African (AFR) AF: 0.307 AC: 12720 AN: 41484

American (AMR) AF: 0.624 AC: 9514 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 2490 AN: 3468

East Asian (EAS) AF: 0.559 AC: 2892 AN: 5170

South Asian (SAS) AF: 0.613 AC: 2956 AN: 4822

European-Finnish (FIN) AF: 0.716 AC: 7578 AN: 10584

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.737 AC: 50128 AN: 67974

Other (OTH) AF: 0.620 AC: 1307 AN: 2108

Alfa AF: 0.633 Hom.: 4453

Bravo AF: 0.571

Asia WGS AF: 0.538 AC: 1873 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.0020
DANN	Benign	0.46
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs229884; hg19: chr7-73722251;