rs767013225

Variant names:

• chr2-24208255-GCTT-G
• rs767013225
• NM_006277.3:c.4657_4659delAAG

Your query was ambiguous. Multiple possible variants found:

• chr2-24208255-GCTT-G
• chr2-24208255-GCTT-GCTTCTT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 1P and 5B. PM4_Supporting BP6 BS2

The NM_006277.3(ITSN2):​c.4657_4659delAAG​(p.Lys1553del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.000255 in 1,612,426 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00027 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00025 (2 hom.)
• Consequence: ITSN2 NM_006277.3 conservative_inframe_deletion
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 5.70
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_006277.3. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 2-24208255-GCTT-G is Benign according to our data. Variant chr2-24208255-GCTT-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3350968.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006277.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITSN2	NM_006277.3	MANE Select	c.4657_4659delAAG	p.Lys1553del	conservative_inframe_deletion	Exon 37 of 40	NP_006268.2	Q9NZM3-1
	ITSN2	NM_001348181.2		c.4615_4617delAAG	p.Lys1539del	conservative_inframe_deletion	Exon 38 of 41	NP_001335110.1
	ITSN2	NM_019595.4		c.4576_4578delAAG	p.Lys1526del	conservative_inframe_deletion	Exon 36 of 39	NP_062541.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITSN2	ENST00000355123.9	TSL:1 MANE Select	c.4657_4659delAAG	p.Lys1553del	conservative_inframe_deletion	Exon 37 of 40	ENSP00000347244.4	Q9NZM3-1
	ITSN2	ENST00000361999.7	TSL:1	c.4576_4578delAAG	p.Lys1526del	conservative_inframe_deletion	Exon 36 of 39	ENSP00000354561.2	Q9NZM3-2
	ITSN2	ENST00000905943.1		c.4618_4620delAAG	p.Lys1540del	conservative_inframe_deletion	Exon 37 of 40	ENSP00000576002.1

Frequencies

GnomAD3 genomes AF: 0.000270 AC: 41 AN: 151948 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000194

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000774

Gnomad SAS AF: 0.000624

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000324

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000299 AC: 75 AN: 250616 AF XY: 0.000288

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000652

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000202

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000253 AC: 370 AN: 1460360 Hom.: 2 AF XY: 0.000270 AC XY: 196 AN XY: 726560

African (AFR) AF: 0.000329 AC: 11 AN: 33474

American (AMR) AF: 0.000336 AC: 15 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39698

South Asian (SAS) AF: 0.000522 AC: 45 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52124

Middle Eastern (MID) AF: 0.00364 AC: 21 AN: 5766

European-Non Finnish (NFE) AF: 0.000232 AC: 258 AN: 1111850

Other (OTH) AF: 0.000182 AC: 11 AN: 60362

GnomAD4 genome AF: 0.000270 AC: 41 AN: 152066 Hom.: 0 Cov.: 31 AF XY: 0.000323 AC XY: 24 AN XY: 74336

African (AFR) AF: 0.000193 AC: 8 AN: 41454

American (AMR) AF: 0.000196 AC: 3 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000776 AC: 4 AN: 5154

South Asian (SAS) AF: 0.000624 AC: 3 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000324 AC: 22 AN: 67962

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000452 Hom.: 0

Bravo AF: 0.000298

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ITSN2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.7
Mutation Taster		=53/47	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs767013225; hg19: chr2-24431124;