Variant 9-19528120-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_020344.4(SLC24A2):c.1498C>G(p.Pro500Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000695 in 1,439,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SLC24A2
NM_020344.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.20

Variant links:

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]

SLC24A2 links:

LOC105375988 (HGNC:):

LOC105375988 links:

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ACMG classification

Classification made for transcript

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=0.2991123).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC24A2	NM_020344.4 linkuse as main transcript	c.1498C>G	p.Pro500Ala	missense_variant	9/11	ENST00000341998.7
LOC105375988	XR_007061431.1 linkuse as main transcript	n.693-25986G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC24A2	ENST00000341998.7 linkuse as main transcript	c.1498C>G	p.Pro500Ala	missense_variant	9/11	1	NM_020344.4	P3	Q9UI40-1
SLC24A2	ENST00000286344.4 linkuse as main transcript	c.1447C>G	p.Pro483Ala	missense_variant	8/10	1		A1	Q9UI40-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.95e-7

AC:

AN:

1439842

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

713674

show subpopulations

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:

9.09e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jun 09, 2022

The c.1498C>G (p.P500A) alteration is located in exon 8 (coding exon 8) of the SLC24A2 gene. This alteration results from a C to G substitution at nucleotide position 1498, causing the proline (P) at amino acid position 500 to be replaced by an alanine (A). 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

0.25

BayesDel_addAF

Uncertain

0.097

BayesDel_noAF

Benign

-0.10

Cadd

Benign

Dann

Benign

0.78

DEOGEN2

Uncertain

0.61

D;.

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.037

MetaRNN

Benign

0.30

T;T

MetaSVM

Benign

-0.36

MutationAssessor

Uncertain

2.0

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-3.8

D;D

REVEL

Uncertain

0.37

Sift

Benign

0.42

T;T

Sift4G

Benign

0.59

T;T

Polyphen

0.17

B;B

Vest4

0.46

MutPred

0.35

Gain of catalytic residue at P500 (P = 0.0847);.;

MVP

0.93

MPC

0.10

ClinPred

0.27

GERP RS

6.2

Varity_R

0.32

gMVP

0.88

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over