rs868936675

Variant names:

• chr7-74338850-C-A
• rs868936675
• NM_003388.5:c.524C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-74338850-C-A
• chr7-74338850-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003388.5(CLIP2):​c.524C>A​(p.Thr175Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLIP2 NM_003388.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.29

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21426865).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLIP2	NM_003388.5	c.524C>A	p.Thr175Lys	missense_variant	Exon 3 of 17	ENST00000223398.11	NP_003379.4
CLIP2	NM_032421.3	c.524C>A	p.Thr175Lys	missense_variant	Exon 3 of 16		NP_115797.2
CLIP2	XM_047420800.1	c.524C>A	p.Thr175Lys	missense_variant	Exon 3 of 13		XP_047276756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLIP2	ENST00000223398.11	c.524C>A	p.Thr175Lys	missense_variant	Exon 3 of 17	5	NM_003388.5	ENSP00000223398.6
CLIP2	ENST00000361545.9	c.524C>A	p.Thr175Lys	missense_variant	Exon 3 of 16	1		ENSP00000355151.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.0011	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.21	.;T;T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.010
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.82	T;T;.
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	0.81	L;L;L
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.5	N;N;N
REVEL	Benign	0.22
Sift	Benign	0.036	D;T;T
Sift4G	Uncertain	0.056	T;T;T
Polyphen		0.43	B;B;B
Vest4		0.45
MutPred		0.35		Gain of solvent accessibility (P = 0.0012);Gain of solvent accessibility (P = 0.0012);Gain of solvent accessibility (P = 0.0012);
MVP		0.58
MPC		0.98
ClinPred		0.49	T
GERP RS		3.9
Varity_R		0.15
gMVP		0.47

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: rs868936675; hg19: chr7-73753180; COSMIC: COSV56282058;