Genetic Variant ENST00000406921.7:c.*492G>T (chr2-24220402-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000406921.7(ITSN2):c.*492G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 983,806 control chromosomes in the GnomAD database, including 256,942 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.77 ( 45851 hom., cov: 33)

Exomes 𝑓: 0.71 ( 211091 hom. )

Consequence

ITSN2
ENST00000406921.7 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0390

Publications

16 publications found

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:

ENSG00000242628 (HGNC:):

ENSG00000242628 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000406921.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ITSN2	NM_006277.3	MANE Select	c.3699+543G>T	intron	N/A	NP_006268.2
ITSN2	NM_147152.3		c.*492G>T	3_prime_UTR	Exon 30 of 30	NP_671494.2
ITSN2	NM_001348181.2		c.3657+543G>T	intron	N/A	NP_001335110.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ITSN2	ENST00000406921.7	TSL:1	c.*492G>T	3_prime_UTR	Exon 30 of 30	ENSP00000384499.3
ITSN2	ENST00000355123.9	TSL:1 MANE Select	c.3699+543G>T	intron	N/A	ENSP00000347244.4
ITSN2	ENST00000361999.7	TSL:1	c.3618+543G>T	intron	N/A	ENSP00000354561.2

Frequencies

GnomAD3 genomes

AF:

0.774

AC:

117715

AN:

152092

Hom.:

45814

Cov.:

show subpopulations

Gnomad AFR

AF:

0.831

Gnomad AMI

AF:

0.775

Gnomad AMR

AF:

0.815

Gnomad ASJ

AF:

0.751

Gnomad EAS

AF:

0.845

Gnomad SAS

AF:

0.769

Gnomad FIN

AF:

0.790

Gnomad MID

AF:

0.772

Gnomad NFE

AF:

0.724

Gnomad OTH

AF:

0.781

GnomAD4 exome

AF:

0.712

AC:

591849

AN:

831596

Hom.:

211091

Cov.:

AF XY:

0.711

AC XY:

273056

AN XY:

384130

show subpopulations

African (AFR)

AF:

0.832

AC:

13124

AN:

15768

American (AMR)

AF:

0.860

AC:

850

AN:

988

Ashkenazi Jewish (ASJ)

AF:

0.762

AC:

3940

AN:

5172

East Asian (EAS)

AF:

0.844

AC:

3052

AN:

3616

South Asian (SAS)

AF:

0.770

AC:

12640

AN:

16422

European-Finnish (FIN)

AF:

0.752

AC:

221

AN:

294

Middle Eastern (MID)

AF:

0.773

AC:

1249

AN:

1616

European-Non Finnish (NFE)

AF:

0.706

AC:

536913

AN:

760458

Other (OTH)

AF:

0.728

AC:

19860

AN:

27262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

7912

15824

23737

31649

39561

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18536

37072

55608

74144

92680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.774

AC:

117806

AN:

152210

Hom.:

45851

Cov.:

AF XY:

0.778

AC XY:

57922

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.831

AC:

34497

AN:

41530

American (AMR)

AF:

0.815

AC:

12469

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.751

AC:

2606

AN:

3472

East Asian (EAS)

AF:

0.845

AC:

4365

AN:

5168

South Asian (SAS)

AF:

0.768

AC:

3704

AN:

4820

European-Finnish (FIN)

AF:

0.790

AC:

8379

AN:

10612

Middle Eastern (MID)

AF:

0.762

AC:

224

AN:

294

European-Non Finnish (NFE)

AF:

0.724

AC:

49198

AN:

67994

Other (OTH)

AF:

0.783

AC:

1657

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1383

2765

4148

5530

6913

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

860

1720

2580

3440

4300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.742

Hom.:

172084

Bravo

AF:

0.778

Asia WGS

AF:

0.827

AC:

2874

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

5.1

(source)

DANN

Benign

0.79

PhyloP100

0.039

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over