chr9-19619685-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_020344.4(SLC24A2):c.977C>T(p.Pro326Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000731 in 1,613,220 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000073 ( 0 hom. )
Consequence
SLC24A2
NM_020344.4 missense
NM_020344.4 missense
Scores
6
10
3
Clinical Significance
Conservation
PhyloP100: 9.96
Genes affected
SLC24A2 (HGNC:10976): (solute carrier family 24 member 2) This gene encodes a member of the calcium/cation antiporter superfamily of transport proteins. The encoded protein belongs to the SLC24 branch of exchangers, which can mediate the extrusion of one Ca2+ ion and one K+ ion in exchange for four Na+ ions. This family member is a retinal cone/brain exchanger that can mediate a light-induced decrease in free Ca2+ concentration. This protein may also play a neuroprotective role during ischemic brain injury. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC24A2 | NM_020344.4 | c.977C>T | p.Pro326Leu | missense_variant | 4/11 | ENST00000341998.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC24A2 | ENST00000341998.7 | c.977C>T | p.Pro326Leu | missense_variant | 4/11 | 1 | NM_020344.4 | P3 | |
SLC24A2 | ENST00000286344.4 | c.977C>T | p.Pro326Leu | missense_variant | 4/10 | 1 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000789 AC: 12AN: 152168Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000797 AC: 20AN: 250830Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135548
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GnomAD4 exome AF: 0.0000726 AC: 106AN: 1460934Hom.: 0 Cov.: 31 AF XY: 0.0000867 AC XY: 63AN XY: 726836
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GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152286Hom.: 0 Cov.: 33 AF XY: 0.0000940 AC XY: 7AN XY: 74472
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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 | May 11, 2022 | The c.977C>T (p.P326L) alteration is located in exon 3 (coding exon 3) of the SLC24A2 gene. This alteration results from a C to T substitution at nucleotide position 977, causing the proline (P) at amino acid position 326 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Uncertain
D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Benign
T;T
Polyphen
D;D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at