NM_024675.4:c.3202-9C>T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_024675.4(PALB2):c.3202-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,612,706 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_024675.4 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 151962Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 251236Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135820
GnomAD4 exome AF: 0.0000233 AC: 34AN: 1460744Hom.: 0 Cov.: 31 AF XY: 0.0000261 AC XY: 19AN XY: 726792
GnomAD4 genome AF: 0.0000197 AC: 3AN: 151962Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74214
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1Benign:1
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The c.3202-9C>T intronic alteration consists of a C to T substitution 9 nucleotides before coding exon 12 in the PALB2 gene. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not specified Benign:1
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Pancreatic cancer, susceptibility to, 3 Benign:1
The PALB2 c.3202-9C>T variant was not identified in the literature nor was it identified in LOVD 3.0. The variant was identified in dbSNP (ID: rs757444247) as “With Likely benign” allele, and in ClinVar (classified likely benign by Invitae, GeneDx, and Color). The variant was identified in control databases in 8 of 246052 chromosomes at a frequency of 0.00003 (Genome Aggregation Database Feb 27, 2017) in the following populations: European Non-Finnish in 1 of 111588 chromosomes (freq: 0.000009), East Asian in 2 of 17236 chromosomes (freq: 0.0001), and South Asian in 5 of 30764 chromosomes (freq: 0.0002), but not in the African, Other, Latino, Ashkenazi Jewish, and Finnish populations. The c.3202-9C>T variant is located in the 3' splice region but does not affect the invariant -1 and -2 positions. Positions -3 and -5 to -12 are part of the splicing consensus sequence and variants involving these positions sometimes affect splicing; however, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. -
not provided Benign:1
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Familial cancer of breast Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at