2-27137623-A-G

Position:

• chr2-27137623-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000335524.7(PRR30):​c.707T>C​(p.Leu236Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000754 in 1,459,586 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: PRR30 ENST00000335524.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.10

Genes affected

PRR30 (HGNC:28677): (proline rich 30)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRR30	NM_178553.4	c.707T>C	p.Leu236Pro	missense_variant	3/3	ENST00000335524.7	NP_848648.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRR30	ENST00000335524.7	c.707T>C	p.Leu236Pro	missense_variant	3/3	1	NM_178553.4	ENSP00000335017	P1
PRR30	ENST00000432962.2	c.213T>C	p.Pro71=	synonymous_variant	4/4	3		ENSP00000393468

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000410 AC: 1 AN: 243866 Hom.: 0 AF XY: 0.00000752 AC XY: 1 AN XY: 132980

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: 0.00

Gnomad NFE exome AF: 0.00000926

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000754 AC: 11 AN: 1459586 Hom.: 0 Cov.: 33 AF XY: 0.00000827 AC XY: 6 AN XY: 725952

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: 0.00000990

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000825 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 05, 2022

The c.707T>C (p.L236P) alteration is located in exon 3 (coding exon 1) of the PRR30 gene. This alteration results from a T to C substitution at nucleotide position 707, causing the leucine (L) at amino acid position 236 to be replaced by a proline (P). 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	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.056	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	1.0	D
PROVEAN	Pathogenic	-5.0	D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.016	D
Polyphen		1.0	D
Vest4		0.78
MutPred		0.52		Loss of stability (P = 0.0076);
MVP		0.41
MPC		0.90
ClinPred		0.98	D
GERP RS		4.7
Varity_R		0.88
gMVP		0.87

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

Publications

LitVar

Other links and lift over

dbSNP: rs751095543; hg19: chr2-27360491;