2-24298897-C-T

Variant names:

• chr2-24298897-C-T
• rs6707600
• NM_006277.3:c.1345-83G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006277.3(ITSN2):​c.1345-83G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.98 in 1,338,952 control chromosomes in the GnomAD database, including 642,684 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.98 (72826 hom., cov: 32)
  • Exomes 𝑓: 0.98 (569858 hom.)
• Consequence: ITSN2 NM_006277.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0610
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-24298897-C-T is Benign according to our data. Variant chr2-24298897-C-T is described in ClinVar as Benign. ClinVar VariationId is 1226269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITSN2	NM_006277.3	c.1345-83G>A		intron_variant	Intron 12 of 39	ENST00000355123.9	NP_006268.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITSN2	ENST00000355123.9	c.1345-83G>A		intron_variant	Intron 12 of 39	1	NM_006277.3	ENSP00000347244.4
ITSN2	ENST00000361999.7	c.1345-83G>A		intron_variant	Intron 12 of 38	1		ENSP00000354561.2
ITSN2	ENST00000406921.7	c.1345-83G>A		intron_variant	Intron 12 of 29	1		ENSP00000384499.3
ITSN2	ENST00000412011.5	c.1420-83G>A		intron_variant	Intron 13 of 16	1		ENSP00000391224.1

Frequencies

GnomAD3 genomes AF: 0.978 AC: 148842 AN: 152180 Hom.: 72785 Cov.: 32

Gnomad AFR AF: 0.972

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.977

Gnomad ASJ AF: 0.979

Gnomad EAS AF: 0.992

Gnomad SAS AF: 0.955

Gnomad FIN AF: 0.986

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.981

Gnomad OTH AF: 0.973

GnomAD4 exome AF: 0.980 AC: 1162890 AN: 1186654 Hom.: 569858 AF XY: 0.979 AC XY: 583341 AN XY: 595804

African (AFR) AF: 0.969 AC: 25611 AN: 26418

American (AMR) AF: 0.985 AC: 28945 AN: 29372

Ashkenazi Jewish (ASJ) AF: 0.982 AC: 19486 AN: 19848

East Asian (EAS) AF: 0.984 AC: 37208 AN: 37808

South Asian (SAS) AF: 0.956 AC: 63455 AN: 66362

European-Finnish (FIN) AF: 0.987 AC: 40547 AN: 41074

Middle Eastern (MID) AF: 0.963 AC: 4458 AN: 4628

European-Non Finnish (NFE) AF: 0.981 AC: 893698 AN: 910646

Other (OTH) AF: 0.980 AC: 49482 AN: 50498

GnomAD4 genome AF: 0.978 AC: 148941 AN: 152298 Hom.: 72826 Cov.: 32 AF XY: 0.978 AC XY: 72827 AN XY: 74466

African (AFR) AF: 0.972 AC: 40378 AN: 41562

American (AMR) AF: 0.977 AC: 14947 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.979 AC: 3399 AN: 3472

East Asian (EAS) AF: 0.992 AC: 5146 AN: 5190

South Asian (SAS) AF: 0.954 AC: 4611 AN: 4832

European-Finnish (FIN) AF: 0.986 AC: 10452 AN: 10600

Middle Eastern (MID) AF: 0.983 AC: 289 AN: 294

European-Non Finnish (NFE) AF: 0.981 AC: 66752 AN: 68028

Other (OTH) AF: 0.973 AC: 2056 AN: 2112

Alfa AF: 0.980 Hom.: 154897

Bravo AF: 0.978

Asia WGS AF: 0.971 AC: 3374 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.55
PhyloP100		-0.061
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6707600; hg19: chr2-24521766;