rs2521501

Variant names:

• chr15-90894158-A-C
• rs2521501
• NM_002005.4:c.2326+100A>C

Your query was ambiguous. Multiple possible variants found:

• chr15-90894158-A-C
• chr15-90894158-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002005.4(FES):​c.2326+100A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,382,454 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 8.1e-7 (0 hom.)
• Consequence: FES NM_002005.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.735
• Publications: 114 publications found

Genes affected

FES (HGNC:3657): (FES proto-oncogene, tyrosine kinase) This gene encodes the human cellular counterpart of a feline sarcoma retrovirus protein with transforming capabilities. The gene product has tyrosine-specific protein kinase activity and that activity is required for maintenance of cellular transformation. Its chromosomal location has linked it to a specific translocation event identified in patients with acute promyelocytic leukemia but it is also involved in normal hematopoiesis as well as growth factor and cytokine receptor signaling. Alternative splicing results in multiple variants encoding different isoforms.[provided by RefSeq, Jan 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FES	NM_002005.4	c.2326+100A>C		intron_variant	Intron 18 of 18	ENST00000328850.8	NP_001996.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FES	ENST00000328850.8	c.2326+100A>C		intron_variant	Intron 18 of 18	1	NM_002005.4	ENSP00000331504.3

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152100 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 8.13e-7 AC: 1 AN: 1230354 Hom.: 0 AF XY: 0.00000163 AC XY: 1 AN XY: 613020

African (AFR) AF: 0.0000354 AC: 1 AN: 28212

American (AMR) AF: 0.00 AC: 0 AN: 35560

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20800

East Asian (EAS) AF: 0.00 AC: 0 AN: 38322

South Asian (SAS) AF: 0.00 AC: 0 AN: 72230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5176

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 938194

Other (OTH) AF: 0.00 AC: 0 AN: 52228

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152100 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74288

African (AFR) AF: 0.000121 AC: 5 AN: 41390

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 411

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	4.6
DANN	Benign	0.61
PhyloP100		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs2521501; hg19: chr15-91437388;