14-21523454-CG-GA

Variant names:

• chr14-21523454-CG-GA
• NM_001364564.1:c.2267_2268delCGinsTC
• SALL2 p.Pro756Leu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001364564.1(SALL2):​c.2267_2268delCGinsTC​(p.Pro756Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P756R) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SALL2 NM_001364564.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• Publications: 0 publications found

Genes affected

SALL2 (HGNC:10526): (spalt like transcription factor 2) This gene encodes a protein containing multiple zinc finger domains. The encoded protein functions in optical fissure closure during development of the eye in the embryo. Mutations in this gene are associated with ocular coloboma. [provided by RefSeq, Jul 2016]

SALL2 Gene-Disease associations (from GenCC):

• coloboma, ocular, autosomal recessive

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364564.1. 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
	SALL2	NM_001364564.1	MANE Select	c.2267_2268delCGinsTC	p.Pro756Leu	missense	N/A	NP_001351493.1	F5H433
	SALL2	NM_005407.3		c.2273_2274delCGinsTC	p.Pro758Leu	missense	N/A	NP_005398.2	Q9Y467-1
	SALL2	NM_001291446.2		c.1868_1869delCGinsTC	p.Pro623Leu	missense	N/A	NP_001278375.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL2	ENST00000537235.2	TSL:2 MANE Select	c.2267_2268delCGinsTC	p.Pro756Leu	missense	N/A	ENSP00000438493.2	F5H433
	SALL2	ENST00000614342.1	TSL:1	c.2273_2274delCGinsTC	p.Pro758Leu	missense	N/A	ENSP00000483562.1	Q9Y467-1
	SALL2	ENST00000611430.4	TSL:1	c.386-1211_386-1210delCGinsTC		intron	N/A	ENSP00000484460.1	Q9Y467-3

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2

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: chr14-21991588;