Variant chr17-8369465-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001304947.3(KRBA2):c.902A>T(p.His301Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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: 0.0000062 ( 0 hom. )

Consequence

KRBA2
NM_001304947.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.508

Variant links:

Genes affected

KRBA2 (HGNC:26989): (KRAB-A domain containing 2) Predicted to enable nucleic acid binding activity. Predicted to be involved in DNA integration and regulation of transcription, DNA-templated. [provided by Alliance of Genome Resources, Apr 2022]

KRBA2 links:

ENSG00000263809 (HGNC:):

ENSG00000263809 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40253988).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRBA2	NM_001304947.3 linkuse as main transcript	c.902A>T	p.His301Leu	missense_variant	2/2	ENST00000396267.3	NP_001291876.1	Q6ZNG9A8MX02
KRBA2	NM_213597.3 linkuse as main transcript	c.1148A>T	p.His383Leu	missense_variant	2/2		NP_998762.1	Q6ZNG9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KRBA2	ENST00000396267.3 linkuse as main transcript	c.902A>T	p.His301Leu	missense_variant	2/2	2	NM_001304947.3	ENSP00000379565.3	A8MX02
ENSG00000263809	ENST00000582471.1 linkuse as main transcript	n.*1885A>T		non_coding_transcript_exon_variant	6/6	5		ENSP00000463847.1	J3QQQ9
ENSG00000263809	ENST00000582471.1 linkuse as main transcript	n.*1885A>T		3_prime_UTR_variant	6/6	5		ENSP00000463847.1	J3QQQ9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461750

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 25, 2024

The c.1148A>T (p.H383L) alteration is located in exon 2 (coding exon 2) of the KRBA2 gene. This alteration results from a A to T substitution at nucleotide position 1148, causing the histidine (H) at amino acid position 383 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.061

.;T;T;T;.

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.42

.;T;T;.;T

M_CAP

Benign

0.0027

MetaRNN

Benign

0.40

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.6

.;.;L;L;.

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-4.0

.;D;D;.;.

REVEL

Benign

0.048

Sift

Benign

0.18

.;T;T;.;.

Sift4G

Benign

0.20

.;T;T;.;.

Polyphen

0.034

.;.;B;B;.

Vest4

0.22, 0.23

MutPred

0.76

.;.;Loss of methylation at K386 (P = 0.1043);Loss of methylation at K386 (P = 0.1043);.;

MVP

0.26

MPC

0.30

ClinPred

0.077

GERP RS

1.7

Varity_R

0.11

gMVP

0.28

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over