5-64690815-C-G

Variant names:

• chr5-64690815-G-G
• ENST00000389074.6:c.

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The ENST00000389074.6(SHISAL2B):​c. variant causes a splice donor, intron change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SHISAL2B ENST00000389074.6 splice_donor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.31
• Publications: 0 publications found

Genes affected

SHISAL2B (HGNC:34236): (shisa like 2B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.6459627 fraction of the gene. Cryptic splice site detected, with MaxEntScore 8.1, offset of 0 (no position change), new splice context is: cagGTgggc. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000389074.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHISAL2B	ENST00000389074.6	TSL:2 MANE Select	c.		splice_donor intron	N/A	ENSP00000373726.5	A6NKW6
	SHISAL2B	ENST00000506473.5	TSL:2	n.		splice_donor intron	N/A	ENSP00000426145.1	D6RH14
	SHISAL2B	ENST00000509189.5	TSL:2	n.		splice_donor intron	N/A	ENSP00000426194.1	D6RH14

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-63986642;