Genetic Variant SPRR2D:p.Val57Glu (chr1-153040177-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006945.5(SPRR2D):c.170T>A(p.Val57Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V57G) has been classified as Uncertain significance.

Frequency

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

Consequence

SPRR2D
NM_006945.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.656

Publications

4 publications found

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]

SPRR2D links:

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ACMG classification

Classification was made for transcript

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=0.204963).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006945.5. 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
	SPRR2D	NM_006945.5	MANE Select	c.170T>A	p.Val57Glu	missense	Exon 2 of 2	NP_008876.3
	SPRR2D	NM_001382248.1		c.170T>A	p.Val57Glu	missense	Exon 2 of 2	NP_001369177.1	P22532

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPRR2D	ENST00000360379.4	TSL:1 MANE Select	c.170T>A	p.Val57Glu	missense	Exon 2 of 2	ENSP00000353542.3	P22532
SPRR2D	ENST00000368756.1	TSL:2	c.170T>A	p.Val57Glu	missense	Exon 3 of 3	ENSP00000357745.1	P22532
SPRR2D	ENST00000368757.1	TSL:3	c.170T>A	p.Val57Glu	missense	Exon 2 of 2	ENSP00000357746.1	P22532

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

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

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251116

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152110

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41416

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.042

Eigen

Benign

-0.033

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.37

M_CAP

Benign

0.0075

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.0

PhyloP100

0.66

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.13

Sift4G

Benign

0.89

Polyphen

0.99

Vest4

0.51

MutPred

0.12

Loss of catalytic residue at V57 (P = 0.0261)

MVP

0.46

MPC

0.78

ClinPred

0.87

GERP RS

3.4

Varity_R

0.47

gMVP

0.0020

Mutation Taster

=86/14

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over