2-24209269-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.4474-48G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,582,210 control chromosomes in the GnomAD database, including 49,494 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (3108 hom., cov: 32)
  • Exomes 𝑓: 0.25 (46386 hom.)
• Consequence: ITSN2 NM_006277.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.119

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=-0.71).
• BP6: Variant 2-24209269-C-T is Benign according to our data. Variant chr2-24209269-C-T is described in ClinVar as [Benign]. Clinvar id is 1276591.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITSN2	NM_006277.3	c.4474-48G>A		intron_variant		ENST00000355123.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITSN2	ENST00000355123.9	c.4474-48G>A		intron_variant		1	NM_006277.3	P2
ITSN2	ENST00000361999.7	c.4393-48G>A		intron_variant		1		A2
ITSN2	ENST00000427234.5	c.131+549G>A		intron_variant, NMD_transcript_variant		3
ITSN2	ENST00000479575.1	n.513-48G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27348 AN: 152062 Hom.: 3107 Cov.: 32

Gnomad AFR AF: 0.0558

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.179

GnomAD3 exomes AF: 0.216 AC: 46062 AN: 212938 Hom.: 5271 AF XY: 0.223 AC XY: 25520 AN XY: 114472

Gnomad AFR exome AF: 0.0566

Gnomad AMR exome AF: 0.112

Gnomad ASJ exome AF: 0.245

Gnomad EAS exome AF: 0.160

Gnomad SAS exome AF: 0.199

Gnomad FIN exome AF: 0.212

Gnomad NFE exome AF: 0.286

Gnomad OTH exome AF: 0.232

GnomAD4 exome AF: 0.248 AC: 354516 AN: 1430030 Hom.: 46386 Cov.: 30 AF XY: 0.247 AC XY: 175573 AN XY: 709690

Gnomad4 AFR exome AF: 0.0505

Gnomad4 AMR exome AF: 0.114

Gnomad4 ASJ exome AF: 0.231

Gnomad4 EAS exome AF: 0.118

Gnomad4 SAS exome AF: 0.189

Gnomad4 FIN exome AF: 0.206

Gnomad4 NFE exome AF: 0.272

Gnomad4 OTH exome AF: 0.232

GnomAD4 genome AF: 0.180 AC: 27345 AN: 152180 Hom.: 3108 Cov.: 32 AF XY: 0.177 AC XY: 13131 AN XY: 74374

Gnomad4 AFR AF: 0.0557

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.257

Gnomad4 OTH AF: 0.177

Alfa AF: 0.213 Hom.: 843

Bravo AF: 0.172

Asia WGS AF: 0.140 AC: 488 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	-0.71
Cadd	Benign	7.9
Dann	Benign	0.79

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: rs2303292; hg19: chr2-24432138;