NM_006277.3:c.1724-150A>G

Variant names:

• chr2-24286501-T-C
• rs17733015
• NM_006277.3:c.1724-150A>G

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.1724-150A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 565,334 control chromosomes in the GnomAD database, including 14,498 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3265 hom., cov: 32)
  • Exomes 𝑓: 0.22 (11233 hom.)
• Consequence: ITSN2 NM_006277.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.831
• Publications: 10 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=-0.9).
• BP6: Variant 2-24286501-T-C is Benign according to our data. Variant chr2-24286501-T-C is described in ClinVar as Benign. ClinVar VariationId is 1271628.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

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.1724-150A>G		intron	N/A	NP_006268.2	Q9NZM3-1
	ITSN2	NM_001348181.2		c.1682-150A>G		intron	N/A	NP_001335110.1
	ITSN2	NM_019595.4		c.1724-150A>G		intron	N/A	NP_062541.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITSN2	ENST00000355123.9	TSL:1 MANE Select	c.1724-150A>G		intron	N/A	ENSP00000347244.4	Q9NZM3-1
	ITSN2	ENST00000361999.7	TSL:1	c.1724-150A>G		intron	N/A	ENSP00000354561.2	Q9NZM3-2
	ITSN2	ENST00000406921.7	TSL:1	c.1724-150A>G		intron	N/A	ENSP00000384499.3	Q9NZM3-3

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29289 AN: 152032 Hom.: 3264 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.221 AC: 91404 AN: 413184 Hom.: 11233 AF XY: 0.220 AC XY: 48479 AN XY: 219946

African (AFR) AF: 0.0964 AC: 905 AN: 9388

American (AMR) AF: 0.121 AC: 1407 AN: 11674

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 3130 AN: 14142

East Asian (EAS) AF: 0.0977 AC: 2499 AN: 25574

South Asian (SAS) AF: 0.176 AC: 6030 AN: 34188

European-Finnish (FIN) AF: 0.197 AC: 6955 AN: 35336

Middle Eastern (MID) AF: 0.176 AC: 344 AN: 1952

European-Non Finnish (NFE) AF: 0.253 AC: 65071 AN: 257484

Other (OTH) AF: 0.216 AC: 5063 AN: 23446

GnomAD4 genome AF: 0.192 AC: 29288 AN: 152150 Hom.: 3265 Cov.: 32 AF XY: 0.188 AC XY: 14020 AN XY: 74392

African (AFR) AF: 0.100 AC: 4169 AN: 41548

American (AMR) AF: 0.160 AC: 2444 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 791 AN: 3464

East Asian (EAS) AF: 0.145 AC: 753 AN: 5196

South Asian (SAS) AF: 0.188 AC: 905 AN: 4822

European-Finnish (FIN) AF: 0.196 AC: 2070 AN: 10570

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17498 AN: 67936

Other (OTH) AF: 0.184 AC: 389 AN: 2110

Alfa AF: 0.235 Hom.: 6963

Bravo AF: 0.187

Asia WGS AF: 0.143 AC: 499 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.26
DANN	Benign	0.42
PhyloP100		-0.83
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: rs17733015; hg19: chr2-24509370; COSMIC: COSV61952857;