rs886041044
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001013838.3(CARMIL2):c.871+1G>T variant causes a splice donor, intron change. The variant allele was found at a frequency of 0.00000124 in 1,609,250 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_001013838.3 splice_donor, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152100Hom.: 0 Cov.: 32
GnomAD4 exome AF: 6.86e-7 AC: 1AN: 1457150Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1AN XY: 724322
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152100Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74298
ClinVar
Submissions by phenotype
Severe combined immunodeficiency due to CARMIL2 deficiency Pathogenic:2
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The invariant splice donor c.871+1G>T in CARMIL2 gene has been reported in homozygous state in individualss affected with primary immunodeficiency disorders Schober T, et.al., 2017. The c.871+1G>T variant is absent in gnomAD Exomes. This variant has been reported to the ClinVar database as Pathogenic. Splice AI predicts this variant to cause splice donor loss 0.99 and splice donor gain 0.61. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Pathogenic. -
Combined immunodeficiency Pathogenic:1
Experimentally proven primary immunodeficiency; combined immunodeficiency -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at