rs483352731

Variant names:

• chr2-24205244-C-A
• rs483352731
• NM_006277.3:c.4732G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-24205244-C-A
• chr2-24205244-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006277.3(ITSN2):​c.4732G>T​(p.Ala1578Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ITSN2 NM_006277.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:2
• Conservation: PhyloP100: 7.54
• Publications: 0 publications found

Genes affected

ITSN2 (HGNC:6184): (intersectin 2) This gene encodes a cytoplasmic protein which contains SH3 domains. This protein is a member of a family of proteins involved in clathrin-mediated endocytosis. Intersectin 2 is thought to regulate the formation of clathrin-coated vesicles and also may function in the induction of T cell antigen receptor (TCR) endocytosis. [provided by RefSeq, Jan 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.753

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006277.3. 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
	ITSN2	NM_006277.3	MANE Select	c.4732G>T	p.Ala1578Ser	missense	Exon 38 of 40	NP_006268.2	Q9NZM3-1
	ITSN2	NM_001348181.2		c.4690G>T	p.Ala1564Ser	missense	Exon 39 of 41	NP_001335110.1
	ITSN2	NM_019595.4		c.4651G>T	p.Ala1551Ser	missense	Exon 37 of 39	NP_062541.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITSN2	ENST00000355123.9	TSL:1 MANE Select	c.4732G>T	p.Ala1578Ser	missense	Exon 38 of 40	ENSP00000347244.4	Q9NZM3-1
	ITSN2	ENST00000361999.7	TSL:1	c.4651G>T	p.Ala1551Ser	missense	Exon 37 of 39	ENSP00000354561.2	Q9NZM3-2
	ITSN2	ENST00000905943.1		c.4693G>T	p.Ala1565Ser	missense	Exon 38 of 40	ENSP00000576002.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	2	-	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.75	T
M_CAP	Uncertain	0.21	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Pathogenic	0.79	D
MutationAssessor	Pathogenic	3.1	M
PhyloP100		7.5
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.3	N
REVEL	Pathogenic	0.68
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.015	D
Polyphen		1.0	D
Vest4		0.49
MutPred		0.78		Gain of catalytic residue at A1578 (P = 0.0016)
MVP		0.92
MPC		0.14
ClinPred		0.91	D
GERP RS		4.6
Varity_R		0.36
gMVP		0.65
Mutation Taster		=50/50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs483352731; hg19: chr2-24428113;