NM_000152.5:c.2646+39G>A
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_000152.5(GAA):c.2646+39G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00407 in 1,555,594 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Consequence
NM_000152.5 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00338 AC: 515AN: 152182Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.00301 AC: 610AN: 202470Hom.: 2 AF XY: 0.00322 AC XY: 346AN XY: 107492
GnomAD4 exome AF: 0.00415 AC: 5822AN: 1403294Hom.: 25 Cov.: 34 AF XY: 0.00422 AC XY: 2918AN XY: 690818
GnomAD4 genome AF: 0.00339 AC: 516AN: 152300Hom.: 2 Cov.: 32 AF XY: 0.00334 AC XY: 249AN XY: 74466
ClinVar
Submissions by phenotype
not specified Benign:1
Variant summary: GAA c.2646+39G>A is located at a position not widely known to affect splicing. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. TThe variant allele was found at a frequency of 0.003 in 202470 control chromosomes (including 2 homozygotes), predominantly at a frequency of 0.0048 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 1.14 fold of the estimated maximal expected allele frequency for a pathogenic variant in GAA causing Glycogen Storage Disease, Type 2 (Pompe Disease) phenotype (0.0042), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. To our knowledge, no occurrence of c.2646+39G>A in individuals affected with Glycogen Storage Disease, Type 2 (Pompe Disease) and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at