chr2-287670-G-A

Position:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001002919.3(ALKAL2):​c.166C>T​(p.His56Tyr) 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. 13/19 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

2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.553
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0585593).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ALKAL2NM_001002919.3 linkuse as main transcriptc.166C>T p.His56Tyr missense_variant 2/6 ENST00000403610.9 NP_001002919.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ALKAL2ENST00000403610.9 linkuse as main transcriptc.166C>T p.His56Tyr missense_variant 2/61 NM_001002919.3 ENSP00000384604.3 Q6UX46-1
ALKAL2ENST00000452023.1 linkuse as main transcriptc.166C>T p.His56Tyr missense_variant 2/53 ENSP00000389939.1 A0A0B4J1W8
ALKAL2ENST00000401489.6 linkuse as main transcriptc.16C>T p.His6Tyr missense_variant 1/53 ENSP00000385214.2 H0Y3U4
ENSG00000228643ENST00000427831.1 linkuse as main transcriptn.164+556G>A intron_variant 3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1332334
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
657162
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.:
33

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 submitterclinical testingAmbry GeneticsFeb 06, 2023The c.166C>T (p.H56Y) 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 166, causing the histidine (H) at amino acid position 56 to be replaced by a tyrosine (Y). 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
0.10
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
0.21
DANN
Benign
0.86
DEOGEN2
Benign
0.031
T;.
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.0092
N
LIST_S2
Benign
0.29
T;T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.059
T;T
MetaSVM
Benign
-0.97
T
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-1.2
N;N
REVEL
Benign
0.062
Sift
Benign
0.094
T;T
Sift4G
Uncertain
0.042
D;D
Polyphen
0.0
B;.
Vest4
0.14
MutPred
0.13
Loss of disorder (P = 0.0228);Loss of disorder (P = 0.0228);
MVP
0.014
MPC
0.21
ClinPred
0.10
T
GERP RS
-9.3
Varity_R
0.089
gMVP
0.20

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: chr2-287670; API