rs587777686

Positions:

• chr8-47789188-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_006904.7(PRKDC):​c.10721C>T​(p.Ala3574Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PRKDC NM_006904.7 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.20

Genes affected

PRKDC (HGNC:9413): (protein kinase, DNA-activated, catalytic subunit) This gene encodes the catalytic subunit of the DNA-dependent protein kinase (DNA-PK). It functions with the Ku70/Ku80 heterodimer protein in DNA double strand break repair and recombination. The protein encoded is a member of the PI3/PI4-kinase family.[provided by RefSeq, Jul 2010]

PRKDC (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 8-47789188-G-A is Pathogenic according to our data. Variant chr8-47789188-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 154323.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKDC	NM_006904.7	c.10721C>T	p.Ala3574Val	missense_variant	75/86	ENST00000314191.7	NP_008835.5
PRKDC	NM_001081640.2	c.10721C>T	p.Ala3574Val	missense_variant	75/85		NP_001075109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKDC	ENST00000314191.7	c.10721C>T	p.Ala3574Val	missense_variant	75/86	1	NM_006904.7	ENSP00000313420.3
PRKDC	ENST00000338368.7	c.10721C>T	p.Ala3574Val	missense_variant	75/85	1		ENSP00000345182.4
PRKDC	ENST00000697603.1	c.3398C>T	p.Ala1133Val	missense_variant	22/33			ENSP00000513358.1
PRKDC	ENST00000697602.1	n.1294C>T		non_coding_transcript_exon_variant	7/18

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Severe combined immunodeficiency due to DNA-PKcs deficiency Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 01, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.35	T;.
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.0034	T
MetaRNN	Uncertain	0.57	D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Pathogenic	3.0	M;M
PrimateAI	Uncertain	0.55	T
REVEL	Benign	0.15
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.95	P;.
Vest4		0.77
MutPred		0.36		Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);
MVP		0.69
MPC		0.65
ClinPred		0.99	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.58
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

Other links and lift over

dbSNP: rs587777686; hg19: chr8-48701749;