2-24209342-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006277.3(ITSN2):c.4474-121G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.903 in 1,106,766 control chromosomes in the GnomAD database, including 453,406 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.85 (56307 hom., cov: 32)
  • Exomes 𝑓: 0.91 (397099 hom.)
• Consequence: ITSN2 NM_006277.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.32

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 2-24209342-C-T is Benign according to our data. Variant chr2-24209342-C-T is described in ClinVar as [Benign]. Clinvar id is 1264044.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.912 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITSN2	NM_006277.3	c.4474-121G>A		intron_variant		ENST00000355123.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITSN2	ENST00000355123.9	c.4474-121G>A		intron_variant		1	NM_006277.3	P2
ITSN2	ENST00000361999.7	c.4393-121G>A		intron_variant		1		A2
ITSN2	ENST00000427234.5	c.131+476G>A		intron_variant, NMD_transcript_variant		3
ITSN2	ENST00000479575.1	n.513-121G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.854 AC: 129912 AN: 152100 Hom.: 56297 Cov.: 32

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.892

Gnomad AMR AF: 0.905

Gnomad ASJ AF: 0.886

Gnomad EAS AF: 0.918

Gnomad SAS AF: 0.922

Gnomad FIN AF: 0.946

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.918

Gnomad OTH AF: 0.864

GnomAD4 exome AF: 0.911 AC: 869845 AN: 954548 Hom.: 397099 AF XY: 0.912 AC XY: 440507 AN XY: 483078

Gnomad4 AFR exome AF: 0.679

Gnomad4 AMR exome AF: 0.912

Gnomad4 ASJ exome AF: 0.890

Gnomad4 EAS exome AF: 0.914

Gnomad4 SAS exome AF: 0.927

Gnomad4 FIN exome AF: 0.943

Gnomad4 NFE exome AF: 0.917

Gnomad4 OTH exome AF: 0.901

GnomAD4 genome AF: 0.854 AC: 129963 AN: 152218 Hom.: 56307 Cov.: 32 AF XY: 0.857 AC XY: 63795 AN XY: 74442

Gnomad4 AFR AF: 0.687

Gnomad4 AMR AF: 0.906

Gnomad4 ASJ AF: 0.886

Gnomad4 EAS AF: 0.917

Gnomad4 SAS AF: 0.922

Gnomad4 FIN AF: 0.946

Gnomad4 NFE AF: 0.918

Gnomad4 OTH AF: 0.862

Alfa AF: 0.905 Hom.: 126312

Bravo AF: 0.840

Asia WGS AF: 0.911 AC: 3166 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.11
Dann	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs2303293; hg19: chr2-24432211;