1-153040264-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006945.5(SPRR2D):​c.83C>T​(p.Pro28Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,612,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SPRR2D
NM_006945.5 missense

Scores

1
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.945
Variant links:
Genes affected
SPRR2D (HGNC:11264): (small proline rich protein 2D) Predicted to be involved in keratinization. Predicted to act upstream of or within female gonad development and response to estradiol. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.083173364).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPRR2DNM_006945.5 linkc.83C>T p.Pro28Leu missense_variant Exon 2 of 2 ENST00000360379.4 NP_008876.3 P22532
SPRR2DNM_001382248.1 linkc.83C>T p.Pro28Leu missense_variant Exon 2 of 2 NP_001369177.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SPRR2DENST00000360379.4 linkc.83C>T p.Pro28Leu missense_variant Exon 2 of 2 1 NM_006945.5 ENSP00000353542.3 P22532
SPRR2DENST00000368756.1 linkc.83C>T p.Pro28Leu missense_variant Exon 3 of 3 2 ENSP00000357745.1 P22532
SPRR2DENST00000368757.1 linkc.83C>T p.Pro28Leu missense_variant Exon 2 of 2 3 ENSP00000357746.1 P22532
SPRR2DENST00000368758.3 linkc.83C>T p.Pro28Leu missense_variant Exon 2 of 2 2 ENSP00000357747.3 P22532

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152128
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00110
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:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1460280
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726442
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152128
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 08, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.83C>T (p.P28L) alteration is located in exon 2 (coding exon 1) of the SPRR2D gene. This alteration results from a C to T substitution at nucleotide position 83, causing the proline (P) at amino acid position 28 to be replaced by a leucine (L). 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
Benign
0.096
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
19
DANN
Benign
0.38
DEOGEN2
Benign
0.047
T;T;T;T
Eigen
Benign
-0.68
Eigen_PC
Benign
-0.72
FATHMM_MKL
Benign
0.17
N
LIST_S2
Benign
0.52
.;.;.;T
M_CAP
Benign
0.0036
T
MetaRNN
Benign
0.083
T;T;T;T
MetaSVM
Benign
-1.0
T
PROVEAN
Pathogenic
-5.5
D;D;D;D
REVEL
Benign
0.063
Sift4G
Benign
0.17
T;T;T;T
Polyphen
0.0040
B;B;B;B
Vest4
0.38
MutPred
0.17
Loss of glycosylation at P28 (P = 0.0227);Loss of glycosylation at P28 (P = 0.0227);Loss of glycosylation at P28 (P = 0.0227);Loss of glycosylation at P28 (P = 0.0227);
MVP
0.54
MPC
0.49
ClinPred
0.30
T
GERP RS
2.0
Varity_R
0.42
gMVP
0.0029

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.

Other links and lift over

dbSNP: rs1001513669; hg19: chr1-153012740; COSMIC: COSV64209229; API