rs762622458

Variant names:

• chr3-33538797-C-T
• rs762622458
• NM_001365631.1:c.3550G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001365631.1(CLASP2):​c.3550G>A​(p.Gly1184Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000981 in 1,427,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000098 (0 hom.)
• Consequence: CLASP2 NM_001365631.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.59
• Publications: 0 publications found

Genes affected

CLASP2 (HGNC:17078): (cytoplasmic linker associated protein 2) Enables cytoskeletal protein binding activity; dystroglycan binding activity; and protein tyrosine kinase binding activity. Involved in several processes, including microtubule cytoskeleton organization; positive regulation of extracellular matrix organization; and regulation of supramolecular fiber organization. Located in several cellular components, including basal cortex; cortical microtubule plus-end; and ruffle membrane. Colocalizes with focal adhesion; kinetochore; and microtubule cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0500136).
• BS2: High AC in GnomAdExome4 at 14 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365631.1. 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
	CLASP2	NM_001365631.1	MANE Select	c.3550G>A	p.Gly1184Ser	missense	Exon 33 of 39	NP_001352560.1	A0A804HJG7
	CLASP2	NM_001365628.1		c.3637G>A	p.Gly1213Ser	missense	Exon 34 of 40	NP_001352557.1
	CLASP2	NM_001365629.1		c.3634G>A	p.Gly1212Ser	missense	Exon 34 of 40	NP_001352558.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLASP2	ENST00000682230.1	MANE Select	c.3550G>A	p.Gly1184Ser	missense	Exon 33 of 39	ENSP00000507498.1	A0A804HJG7
	CLASP2	ENST00000468888.6	TSL:5	c.3574G>A	p.Gly1192Ser	missense	Exon 33 of 39	ENSP00000419974.2	E7EW49
	CLASP2	ENST00000399362.8	TSL:5	c.3571G>A	p.Gly1191Ser	missense	Exon 33 of 39	ENSP00000382297.4	E7ERI8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000919 AC: 2 AN: 217704 AF XY: 0.00000848

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000984

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000981 AC: 14 AN: 1427594 Hom.: 0 Cov.: 29 AF XY: 0.0000113 AC XY: 8 AN XY: 708624

African (AFR) AF: 0.00 AC: 0 AN: 31968

American (AMR) AF: 0.00 AC: 0 AN: 37684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24666

East Asian (EAS) AF: 0.0000255 AC: 1 AN: 39182

South Asian (SAS) AF: 0.0000382 AC: 3 AN: 78600

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52462

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5614

European-Non Finnish (NFE) AF: 0.00000637 AC: 7 AN: 1098496

Other (OTH) AF: 0.0000509 AC: 3 AN: 58922

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000828 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	16
DANN	Benign	0.73
DEOGEN2	Benign	0.0067	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.6
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.058
Sift	Benign	0.28	T
Sift4G	Benign	0.85	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.16		Gain of phosphorylation at G1191 (P = 0.0033)
MVP		0.28
MPC		0.45
ClinPred		0.22	T
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=68/32	polymorphism

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: rs762622458; hg19: chr3-33580289;