Genetic Variant HCK:p.Glu110Glu (chr20-32074623-A-G) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_002110.5(HCK):c.330A>G(p.Glu110Glu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00161 in 1,608,494 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 10 hom. )

Consequence

HCK
NM_002110.5 splice_region, synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.69

Variant links:

Genes affected

HCK (HGNC:4840): (HCK proto-oncogene, Src family tyrosine kinase) The protein encoded by this gene is a member of the Src family of tyrosine kinases. This protein is primarily hemopoietic, particularly in cells of the myeloid and B-lymphoid lineages. It may help couple the Fc receptor to the activation of the respiratory burst. In addition, it may play a role in neutrophil migration and in the degranulation of neutrophils. Multiple isoforms with different subcellular distributions are produced due to both alternative splicing and the use of alternative translation initiation codons, including a non-AUG (CUG) codon. [provided by RefSeq, Feb 2010]

HCK links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 20-32074623-A-G is Benign according to our data. Variant chr20-32074623-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3770454.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-32074623-A-G is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=2.69 with no splicing effect.

BS2

High AC in GnomAd4 at 222 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HCK	NM_002110.5 link	c.330A>G	p.Glu110Glu	splice_region_variant, synonymous_variant	Exon 5 of 13	ENST00000375852.5	NP_002101.2	P08631-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HCK	ENST00000375852.5 link	c.330A>G	p.Glu110Glu	splice_region_variant, synonymous_variant	Exon 5 of 13	1	NM_002110.5	ENSP00000365012.3		P08631-1J3KPD6

Frequencies

GnomAD3 genomes

AF:

0.00145

AC:

220

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00996

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00156

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.00196

AC:

493

AN:

251328

Hom.:

AF XY:

0.00239

AC XY:

325

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00107

Gnomad ASJ exome

AF:

0.00367

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00683

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00168

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00163

AC:

2369

AN:

1456306

Hom.:

Cov.:

AF XY:

0.00186

AC XY:

1348

AN XY:

724898

show subpopulations

Gnomad4 AFR exome

AF:

0.000210

Gnomad4 AMR exome

AF:

0.00134

Gnomad4 ASJ exome

AF:

0.00333

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00743

Gnomad4 FIN exome

AF:

0.000169

Gnomad4 NFE exome

AF:

0.00131

Gnomad4 OTH exome

AF:

0.00163

GnomAD4 genome

AF:

0.00146

AC:

222

AN:

152188

Hom.:

Cov.:

AF XY:

0.00159

AC XY:

118

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.00548

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0102

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00157

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00149

Hom.:

Bravo

AF:

0.00127

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.00267

EpiControl

AF:

0.00219

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

HCK: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.80

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over