14-21522047-G-C

Variant names:

• chr14-21522047-G-C
• rs741707
• ENST00000611430.4:c.583C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000611430.4(SALL2):​c.583C>G​(p.Gln195Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,444,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SALL2 ENST00000611430.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980
• Publications: 1 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: AR, Unknown Classification: LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)

ENSG00000257096 (HGNC:):

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11980608).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000611430.4. 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.*657C>G		3_prime_UTR	Exon 2 of 2	NP_001351493.1	F5H433
	SALL2	NM_001291446.2		c.2688C>G	p.Pro896Pro	synonymous	Exon 4 of 4	NP_001278375.1
	SALL2	NM_001291447.2		c.2682C>G	p.Pro894Pro	synonymous	Exon 4 of 4	NP_001278376.1	E7EW59

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL2	ENST00000611430.4	TSL:1	c.583C>G	p.Gln195Glu	missense	Exon 3 of 3	ENSP00000484460.1	Q9Y467-3
	SALL2	ENST00000537235.2	TSL:2 MANE Select	c.*657C>G		3_prime_UTR	Exon 2 of 2	ENSP00000438493.2	F5H433
	SALL2	ENST00000614342.1	TSL:1	c.*657C>G		3_prime_UTR	Exon 2 of 2	ENSP00000483562.1	Q9Y467-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000438 AC: 1 AN: 228516 AF XY: 0.00000794

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: 0.00

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1444188 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 718584

African (AFR) AF: 0.00 AC: 0 AN: 33446

American (AMR) AF: 0.00 AC: 0 AN: 44408

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26058

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85670

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37944

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111024

Other (OTH) AF: 0.00 AC: 0 AN: 60216

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.90
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.098
Sift4G	Pathogenic	0.0	D
Vest4		0.24
MutPred		0.13		Gain of phosphorylation at S199 (P = 0.1113)
MVP		0.40
ClinPred		0.077	T
GERP RS		0.98
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs741707; hg19: chr14-21990181;