Variant 2-287811-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001002919.3(ALKAL2):c.25C>T(p.Leu9Phe) 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. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ALKAL2
NM_001002919.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.17

Variant links:

Genes affected

ALKAL2 (HGNC:27683): (ALK and LTK ligand 2) Enables receptor signaling protein tyrosine kinase activator activity and receptor tyrosine kinase binding activity. Involved in positive regulation of ERK1 and ERK2 cascade; positive regulation of ERK5 cascade; and positive regulation of neuron projection development. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ALKAL2 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23741099).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALKAL2	NM_001002919.3 linkuse as main transcript	c.25C>T	p.Leu9Phe	missense_variant	2/6	ENST00000403610.9	NP_001002919.2
LOC101927262	XR_007085889.1 linkuse as main transcript	n.696+1187G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALKAL2	ENST00000403610.9 linkuse as main transcript	c.25C>T	p.Leu9Phe	missense_variant	2/6	1	NM_001002919.3	ENSP00000384604	P1	Q6UX46-1
	ENST00000427831.1 linkuse as main transcript	n.164+697G>A		intron_variant, non_coding_transcript_variant		3
ALKAL2	ENST00000452023.1 linkuse as main transcript	c.25C>T	p.Leu9Phe	missense_variant	2/5	3		ENSP00000389939

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1193796

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

581218

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

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

Feb 08, 2023

The c.25C>T (p.L9F) alteration is located in exon 2 (coding exon 1) of the FAM150B gene. This alteration results from a C to T substitution at nucleotide position 25, causing the leucine (L) at amino acid position 9 to be replaced by a phenylalanine (F). 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

0.14

BayesDel_addAF

Benign

-0.041

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.035

T;.;.

Eigen

Benign

-0.041

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.38

T;T;T

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.24

T;T;T

MetaSVM

Benign

-0.96

MutationTaster

Benign

0.99

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-1.4

N;.;N

REVEL

Benign

0.066

Sift

Benign

0.035

D;.;D

Sift4G

Benign

0.23

T;D;T

Polyphen

0.95

P;.;.

Vest4

0.35

MutPred

0.35

Loss of disorder (P = 0.0449);Loss of disorder (P = 0.0449);Loss of disorder (P = 0.0449);

MVP

0.12

MPC

0.20

ClinPred

0.77

GERP RS

0.24

Varity_R

0.097

gMVP

0.38

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over