22-37492481-G-A

Variant summary

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

The NM_014550.4(CARD10):​c.2705C>T​(p.Pro902Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000524 in 1,602,244 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

CARD10
NM_014550.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.990
Variant links:
Genes affected
CARD10 (HGNC:16422): (caspase recruitment domain family member 10) The caspase recruitment domain (CARD) is a protein module that consists of 6 or 7 antiparallel alpha helices. It participates in apoptosis signaling through highly specific protein-protein homophilic interactions. Like several other CARD proteins, CARD10 belongs to the membrane-associated guanylate kinase (MAGUK) family and activates NF-kappa-B (NFKB; see MIM 164011) through BCL10 (MIM 603517) (Wang et al., 2001 [PubMed 11259443]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

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=0.0067119002).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CARD10NM_014550.4 linkuse as main transcriptc.2705C>T p.Pro902Leu missense_variant 18/20 ENST00000251973.10 NP_055365.2 Q9BWT7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CARD10ENST00000251973.10 linkuse as main transcriptc.2705C>T p.Pro902Leu missense_variant 18/201 NM_014550.4 ENSP00000251973.5 Q9BWT7-1

Frequencies

GnomAD3 genomes
AF:
0.0000788
AC:
12
AN:
152238
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00212
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000202
AC:
49
AN:
242960
Hom.:
0
AF XY:
0.000197
AC XY:
26
AN XY:
131784
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00264
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000169
GnomAD4 exome
AF:
0.0000497
AC:
72
AN:
1449890
Hom.:
0
Cov.:
32
AF XY:
0.0000458
AC XY:
33
AN XY:
720004
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00169
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.05e-7
Gnomad4 OTH exome
AF:
0.0000669
GnomAD4 genome
AF:
0.0000788
AC:
12
AN:
152354
Hom.:
0
Cov.:
32
AF XY:
0.0000940
AC XY:
7
AN XY:
74506
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00212
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000136
Hom.:
0
Bravo
AF:
0.000140
ExAC
AF:
0.000231
AC:
28
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

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 GeneticsJun 11, 2024The c.2705C>T (p.P902L) alteration is located in exon 18 (coding exon 18) of the CARD10 gene. This alteration results from a C to T substitution at nucleotide position 2705, causing the proline (P) at amino acid position 902 to be replaced by a leucine (L). 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
0.091
BayesDel_addAF
Benign
-0.56
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
18
DANN
Benign
0.60
DEOGEN2
Benign
0.094
T;.;T
Eigen
Benign
-0.61
Eigen_PC
Benign
-0.45
FATHMM_MKL
Benign
0.24
N
LIST_S2
Benign
0.78
.;T;T
M_CAP
Benign
0.0092
T
MetaRNN
Benign
0.0067
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.42
N;.;N
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
-0.48
N;N;N
REVEL
Benign
0.032
Sift
Benign
0.68
T;T;T
Sift4G
Benign
0.75
T;T;T
Polyphen
0.0
B;.;B
Vest4
0.20
MVP
0.37
MPC
0.33
ClinPred
0.019
T
GERP RS
2.8
Varity_R
0.044
gMVP
0.32

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.

Other links and lift over

dbSNP: rs188225081; hg19: chr22-37888488; API