chr17-8369942-G-T

Position:

• chr17-8369942-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001304947.3(KRBA2):​c.425C>A​(p.Thr142Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 33)
• Consequence: KRBA2 NM_001304947.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.03

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]

ENSG00000263809 (HGNC:):

ACMG classification

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=0.31706238).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRBA2	NM_001304947.3	c.425C>A	p.Thr142Asn	missense_variant	2/2	ENST00000396267.3	NP_001291876.1
KRBA2	NM_213597.3	c.671C>A	p.Thr224Asn	missense_variant	2/2		NP_998762.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRBA2	ENST00000396267.3	c.425C>A	p.Thr142Asn	missense_variant	2/2	2	NM_001304947.3	ENSP00000379565.3
ENSG00000263809	ENST00000582471.1	n.*1408C>A		non_coding_transcript_exon_variant	6/6	5		ENSP00000463847.1
ENSG00000263809	ENST00000582471.1	n.*1408C>A		3_prime_UTR_variant	6/6	5		ENSP00000463847.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 25, 2024

The c.671C>A (p.T224N) alteration is located in exon 2 (coding exon 2) of the KRBA2 gene. This alteration results from a C to A substitution at nucleotide position 671, causing the threonine (T) at amino acid position 224 to be replaced by an asparagine (N). 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	Pathogenic	0.87
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	.;T;T;T;.
Eigen	Benign	0.16
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.79	.;T;T;.;T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.32	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	.;.;L;L;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-3.0	.;D;D;.;.
REVEL	Benign	0.10
Sift	Benign	0.040	.;D;D;.;.
Sift4G	Pathogenic	0.0	.;D;D;.;.
Polyphen		0.66	.;.;P;P;.
Vest4		0.43, 0.50
MutPred		0.57		.;.;Loss of methylation at K219 (P = 0.0757);Loss of methylation at K219 (P = 0.0757);.;
MVP		0.42
MPC		0.50
ClinPred		0.86	D
GERP RS		2.6
Varity_R		0.23
gMVP		0.36

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.

Other links and lift over

hg19: chr17-8273260;