NM_001364564.1:c.2264C>T

Variant names:

• chr14-21523458-G-A
• rs1258678521
• NM_001364564.1:c.2264C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001364564.1(SALL2):​c.2264C>T​(p.Ser755Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,614,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S755P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: SALL2 NM_001364564.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.30
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1270909).

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.2264C>T	p.Ser755Leu	missense	Exon 2 of 2	NP_001351493.1	F5H433
	SALL2	NM_005407.3		c.2270C>T	p.Ser757Leu	missense	Exon 2 of 2	NP_005398.2	Q9Y467-1
	SALL2	NM_001291446.2		c.1865C>T	p.Ser622Leu	missense	Exon 3 of 4	NP_001278375.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL2	ENST00000537235.2	TSL:2 MANE Select	c.2264C>T	p.Ser755Leu	missense	Exon 2 of 2	ENSP00000438493.2	F5H433
	SALL2	ENST00000614342.1	TSL:1	c.2270C>T	p.Ser757Leu	missense	Exon 2 of 2	ENSP00000483562.1	Q9Y467-1
	SALL2	ENST00000611430.4	TSL:1	c.386-1214C>T		intron	N/A	ENSP00000484460.1	Q9Y467-3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152170 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251146 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.0000109 AC: 16 AN: 1461846 Hom.: 0 Cov.: 34 AF XY: 0.00000963 AC XY: 7 AN XY: 727220

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.00000989 AC: 11 AN: 1112006

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152170 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74346

African (AFR) AF: 0.00 AC: 0 AN: 41424

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.92	T
PhyloP100		2.3
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.051
Sift	Uncertain	0.011	D
Sift4G	Benign	0.18	T
Polyphen		0.81	P
Vest4		0.18
MutPred		0.32		Loss of phosphorylation at S757 (P = 8e-04)
MVP		0.34
ClinPred		0.24	T
GERP RS		4.8
gMVP		0.25
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1258678521; hg19: chr14-21991592;