21-21335539-A-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_004540.5(NCAM2):c.772A>T(p.Ile258Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,454,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_004540.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NCAM2 | NM_004540.5 | c.772A>T | p.Ile258Leu | missense_variant | 7/18 | ENST00000400546.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NCAM2 | ENST00000400546.6 | c.772A>T | p.Ile258Leu | missense_variant | 7/18 | 1 | NM_004540.5 | P1 | |
NCAM2 | ENST00000284894.8 | c.718A>T | p.Ile240Leu | missense_variant | 6/17 | 5 | |||
NCAM2 | ENST00000461281.1 | n.366A>T | non_coding_transcript_exon_variant | 4/5 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000124 AC: 3AN: 242230Hom.: 0 AF XY: 0.0000152 AC XY: 2AN XY: 131656
GnomAD4 exome AF: 0.00000275 AC: 4AN: 1454124Hom.: 0 Cov.: 30 AF XY: 0.00000415 AC XY: 3AN XY: 723328
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 13, 2021 | The c.772A>T (p.I258L) alteration is located in exon 7 (coding exon 7) of the NCAM2 gene. This alteration results from a A to T substitution at nucleotide position 772, causing the isoleucine (I) at amino acid position 258 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at