Variant 22-21642383-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_022044.3(SDF2L1):c.47G>A(p.Gly16Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000696 in 1,445,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. G16R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00073 ( 0 hom. )

Consequence

SDF2L1
NM_022044.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0540

Variant links:

Genes affected

SDF2L1 (HGNC:10676): (stromal cell derived factor 2 like 1) Enables misfolded protein binding activity. Involved in chaperone cofactor-dependent protein refolding. Located in endoplasmic reticulum. Part of chaperone complex. [provided by Alliance of Genome Resources, Apr 2022]

SDF2L1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.033517927).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDF2L1	NM_022044.3 linkuse as main transcript	c.47G>A	p.Gly16Glu	missense_variant	1/3	ENST00000248958.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDF2L1	ENST00000248958.5 linkuse as main transcript	c.47G>A	p.Gly16Glu	missense_variant	1/3	1	NM_022044.3	P1
SDF2L1	ENST00000466935.1 linkuse as main transcript	n.30G>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.000427

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

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:

0.000867

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000370

AC:

AN:

56790

Hom.:

AF XY:

0.000244

AC XY:

AN XY:

32744

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000969

Gnomad NFE exome

AF:

0.000892

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000728

AC:

941

AN:

1292810

Hom.:

Cov.:

AF XY:

0.000699

AC XY:

443

AN XY:

633880

show subpopulations

Gnomad4 AFR exome

AF:

0.000123

Gnomad4 AMR exome

AF:

0.0000731

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000115

Gnomad4 NFE exome

AF:

0.000883

Gnomad4 OTH exome

AF:

0.000225

GnomAD4 genome

AF:

0.000427

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.000403

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000867

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000281

Hom.:

Bravo

AF:

0.000431

ExAC

AF:

0.000175

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2021

The c.47G>A (p.G16E) alteration is located in exon 1 (coding exon 1) of the SDF2L1 gene. This alteration results from a G to A substitution at nucleotide position 47, causing the glycine (G) at amino acid position 16 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.022

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.81

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.48

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.034

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.43

REVEL

Uncertain

0.41

Sift

Benign

0.43

Sift4G

Benign

1.0

Polyphen

0.079

Vest4

0.41

MVP

0.62

MPC

1.6

ClinPred

0.036

GERP RS

1.1

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.1

Varity_R

0.075

gMVP

0.35

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over