Genetic Variant BLTP2:p.Arg1974Leu (chr17-28616989-C-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_014680.5(BLTP2):c.5921G>T(p.Arg1974Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1974Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

BLTP2
NM_014680.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.34

Publications

0 publications found

Variant links:

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 links:

SPAG5-AS1 (HGNC:41140): (SPAG5 antisense RNA 1)

SPAG5-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.833

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014680.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
BLTP2	NM_014680.5	MANE Select	c.5921G>T	p.Arg1974Leu	missense	Exon 34 of 39	NP_055495.2
BLTP2	NM_001321560.2		c.5918G>T	p.Arg1973Leu	missense	Exon 34 of 39	NP_001308489.1
BLTP2	NM_001363826.1		c.5492G>T	p.Arg1831Leu	missense	Exon 33 of 38	NP_001350755.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BLTP2	ENST00000528896.7	TSL:1 MANE Select	c.5921G>T	p.Arg1974Leu	missense	Exon 34 of 39	ENSP00000436773.2	Q14667-1
SPAG5-AS1	ENST00000414744.2	TSL:1	n.1755C>A		non_coding_transcript_exon	Exon 2 of 2
BLTP2	ENST00000939120.1		c.5918G>T	p.Arg1973Leu	missense	Exon 34 of 39	ENSP00000609179.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459542

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726040

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33440

American (AMR)

AF:

0.00

AC:

AN:

44542

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26100

East Asian (EAS)

AF:

0.00

AC:

AN:

39648

South Asian (SAS)

AF:

0.00

AC:

AN:

86082

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53218

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5488

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1110788

Other (OTH)

AF:

0.00

AC:

AN:

60236

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.070

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0013

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.022

MetaRNN

Pathogenic

0.83

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.1

PhyloP100

7.3

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.96

REVEL

Uncertain

0.39

Sift

Benign

0.44

Sift4G

Uncertain

0.016

Polyphen

1.0

Vest4

0.90

MutPred

0.73

Loss of MoRF binding (P = 0.0199)

MVP

0.62

MPC

1.5

ClinPred

0.78

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.19

gMVP

0.77

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over