Variant 2-24203569-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.711

Variant links:

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]

ITSN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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_single_submitter, 1 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 linkuse as main transcript	c.*57G>C		3_prime_UTR_variant	40/40	ENST00000355123.9

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITSN2	ENST00000355123.9 linkuse as main transcript	c.*57G>C	3_prime_UTR_variant	40/40	1	NM_006277.3	P2	Q9NZM3-1
ITSN2	ENST00000361999.7 linkuse as main transcript	c.*57G>C	3_prime_UTR_variant	39/39	1		A2	Q9NZM3-2
ITSN2	ENST00000478720.1 linkuse as main transcript	n.1330G>C	non_coding_transcript_exon_variant	2/2	2
ITSN2	ENST00000427234.5 linkuse as main transcript	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.:

show subpopulations

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.:

AF XY:

0.0399

AC XY:

27722

AN XY:

693998

show subpopulations

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.:

AF XY:

0.0355

AC XY:

2642

AN XY:

74486

show subpopulations

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.:

Bravo

AF:

0.0268

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over