22-20918264-C-T

Variant names:

• chr22-20918264-C-T
• rs757082169
• NM_005207.4:c.311+19C>T

Variant summary

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

The NM_005207.4(CRKL):​c.311+19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,580 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CRKL NM_005207.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.827
• Publications: 0 publications found

Genes affected

CRKL (HGNC:2363): (CRK like proto-oncogene, adaptor protein) This gene encodes a protein kinase containing SH2 and SH3 (src homology) domains which has been shown to activate the RAS and JUN kinase signaling pathways and transform fibroblasts in a RAS-dependent fashion. It is a substrate of the BCR-ABL tyrosine kinase, plays a role in fibroblast transformation by BCR-ABL, and may be oncogenic.[provided by RefSeq, Jan 2009]

CRKL Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

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=-0.74).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005207.4. 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
	CRKL	NM_005207.4	MANE Select	c.311+19C>T		intron	N/A	NP_005198.1	P46109
	CRKL	NR_156180.2		n.839+19C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRKL	ENST00000354336.8	TSL:1 MANE Select	c.311+19C>T		intron	N/A	ENSP00000346300.3	P46109
	CRKL	ENST00000411769.1	TSL:1	n.311+19C>T		intron	N/A	ENSP00000396646.1	P46109
	CRKL	ENST00000894699.1		c.330C>T	p.Pro110Pro	synonymous	Exon 1 of 3	ENSP00000564758.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458580 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725566

African (AFR) AF: 0.00 AC: 0 AN: 33430

American (AMR) AF: 0.00 AC: 0 AN: 44512

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26042

East Asian (EAS) AF: 0.00 AC: 0 AN: 39654

South Asian (SAS) AF: 0.00 AC: 0 AN: 86138

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51792

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110952

Other (OTH) AF: 0.00 AC: 0 AN: 60296

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	2.5
DANN	Benign	0.76
PhyloP100		-0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs757082169; hg19: chr22-21272552;