rs229870

Positions:

• chr7-74320212-A-G
• chr7-74320212-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_003388.5(CLIP2):​c.121+2545A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00572 in 114,378 control chromosomes in the GnomAD database, including 6 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 0.0057 (6 hom., cov: 26)
• Consequence: CLIP2 NM_003388.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.195

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=-1.01).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00572 (654/114378) while in subpopulation AFR AF= 0.0181 (631/34938). AF 95% confidence interval is 0.0169. There are 6 homozygotes in gnomad4. There are 308 alleles in male gnomad4 subpopulation. Median coverage is 26. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 654 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLIP2	NM_003388.5	c.121+2545A>G		intron_variant		ENST00000223398.11	NP_003379.4
CLIP2	NM_032421.3	c.121+2545A>G		intron_variant			NP_115797.2
CLIP2	XM_047420800.1	c.121+2545A>G		intron_variant			XP_047276756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLIP2	ENST00000223398.11	c.121+2545A>G		intron_variant		5	NM_003388.5	ENSP00000223398	P3
CLIP2	ENST00000361545.9	c.121+2545A>G		intron_variant		1		ENSP00000355151	A1

Frequencies

GnomAD3 genomes AF: 0.00567 AC: 648 AN: 114290 Hom.: 6 Cov.: 26

Gnomad AFR AF: 0.0179

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000252

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000806

Gnomad OTH AF: 0.00329

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

GnomAD4 genome AF: 0.00572 AC: 654 AN: 114378 Hom.: 6 Cov.: 26 AF XY: 0.00551 AC XY: 308 AN XY: 55938

Gnomad4 AFR AF: 0.0181

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000253

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000806

Gnomad4 OTH AF: 0.00327

Alfa AF: 0.000170 Hom.: 0

Asia WGS AF: 0.00319 AC: 11 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.9
DANN	Benign	0.15

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: rs229870; hg19: chr7-73734542;