17-28619702-T-C

Position:

• chr17-28619702-T-C

Variant summary

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

The NM_014680.5(BLTP2):​c.5594A>G​(p.Glu1865Gly) variant causes a missense change. 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: 32)
• Consequence: BLTP2 NM_014680.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.67

Genes affected

BLTP2 (HGNC:28960): (bridge-like lipid transfer protein family member 2) This gene was initially characterized in human as having high expression levels in breast carcinomas and breast cancer cell lines. This gene also has increased expression in prostrate cancer cells relative to normal prostrate tissues. Expression of this gene is negatively regulated by direct binding of the microRNA miR-195 to its 3' UTR. miR-195 has been shown to modulate the invasiveness of prostrate cancer cells and xenograft metastases by downgrading expression of this gene. In mouse, the protein encoded by this gene was identified as an antigen on acute monocytic leukemia cells. In human, alternative splicing results in multiple transcript variants encoding distinct isoforms; some of these isoforms are predicted to contain an RNA pol II promoter FMP27 protein domain and a Golgi-body-localization APT1 domain. [provided by RefSeq, Apr 2017]

BLTP2 (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=0.2795088).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLTP2	NM_014680.5	c.5594A>G	p.Glu1865Gly	missense_variant	31/39	ENST00000528896.7	NP_055495.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BLTP2	ENST00000528896.7	c.5594A>G	p.Glu1865Gly	missense_variant	31/39	1	NM_014680.5	ENSP00000436773.2
BLTP2	ENST00000389003.7	c.5165A>G	p.Glu1722Gly	missense_variant	31/39	5		ENSP00000467716.1
BLTP2	ENST00000579924.6	n.74A>G		non_coding_transcript_exon_variant	1/4	3
BLTP2	ENST00000580395.1	n.275A>G		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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

Sep 03, 2024

The c.5594A>G (p.E1865G) alteration is located in exon 31 (coding exon 31) of the KIAA0100 gene. This alteration results from a A to G substitution at nucleotide position 5594, causing the glutamic acid (E) at amino acid position 1865 to be replaced by a glycine (G). 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	Uncertain	0.51
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0039	T;T;T
Eigen	Benign	-0.060
Eigen_PC	Benign	0.097
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.28	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;.;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-2.1	N;N;.
REVEL	Benign	0.13
Sift	Benign	0.59	T;T;.
Sift4G	Benign	0.26	T;T;T
Polyphen		0.046	B;.;.
Vest4		0.51
MutPred		0.50		Gain of loop (P = 3e-04);.;.;
MVP		0.53
MPC		1.0
ClinPred		0.73	D
GERP RS		4.8
Varity_R		0.18
gMVP		0.61

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

Other links and lift over

dbSNP: rs1597619315; hg19: chr17-26946720;