chr2-24203569-C-G

Position:

• chr2-24203569-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_006277.3(ITSN2):​c.*57G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0392 in 1,555,762 control chromosomes in the GnomAD database, including 1,417 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (131 hom., cov: 32)
  • Exomes 𝑓: 0.040 (1286 hom.)
• Consequence: ITSN2 NM_006277.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.711

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 2-24203569-C-G is Benign according to our data. Variant chr2-24203569-C-G is described in ClinVar as [Benign]. Clinvar id is 1242525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.034 (5184/152332) while in subpopulation NFE AF= 0.0441 (2997/68026). AF 95% confidence interval is 0.0427. There are 131 homozygotes in gnomad4. There are 2642 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 131 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITSN2	NM_006277.3	c.*57G>C		3_prime_UTR_variant	40/40	ENST00000355123.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITSN2	ENST00000355123.9	c.*57G>C		3_prime_UTR_variant	40/40	1	NM_006277.3	P2
ITSN2	ENST00000361999.7	c.*57G>C		3_prime_UTR_variant	39/39	1		A2
ITSN2	ENST00000478720.1	n.1330G>C		non_coding_transcript_exon_variant	2/2	2
ITSN2	ENST00000427234.5	c.*520G>C		3_prime_UTR_variant, NMD_transcript_variant	5/5	3

Frequencies

GnomAD3 genomes AF: 0.0341 AC: 5190 AN: 152214 Hom.: 132 Cov.: 32

Gnomad AFR AF: 0.00740

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0266

Gnomad ASJ AF: 0.0527

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0345

Gnomad FIN AF: 0.0965

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0441

Gnomad OTH AF: 0.0363

GnomAD4 exome AF: 0.0398 AC: 55838 AN: 1403430 Hom.: 1286 Cov.: 27 AF XY: 0.0399 AC XY: 27722 AN XY: 693998

Gnomad4 AFR exome AF: 0.00609

Gnomad4 AMR exome AF: 0.0194

Gnomad4 ASJ exome AF: 0.0530

Gnomad4 EAS exome AF: 0.0000515

Gnomad4 SAS exome AF: 0.0395

Gnomad4 FIN exome AF: 0.0859

Gnomad4 NFE exome AF: 0.0405

Gnomad4 OTH exome AF: 0.0391

GnomAD4 genome AF: 0.0340 AC: 5184 AN: 152332 Hom.: 131 Cov.: 32 AF XY: 0.0355 AC XY: 2642 AN XY: 74486

Gnomad4 AFR AF: 0.00741

Gnomad4 AMR AF: 0.0265

Gnomad4 ASJ AF: 0.0527

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0339

Gnomad4 FIN AF: 0.0965

Gnomad4 NFE AF: 0.0441

Gnomad4 OTH AF: 0.0360

Alfa AF: 0.0227 Hom.: 6

Bravo AF: 0.0268

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 13, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.24
DANN	Benign	0.61

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: rs112277321; hg19: chr2-24426438;