2-27137560-C-T

Variant names:

• chr2-27137560-C-T
• rs377666702
• NM_178553.4:c.770G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_178553.4(PRR30):​c.770G>A​(p.Arg257Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000017 in 1,590,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. R257P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: PRR30 NM_178553.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.327
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.050115317).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178553.4. 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
	PRR30	NM_178553.4	MANE Select	c.770G>A	p.Arg257Gln	missense	Exon 3 of 3	NP_848648.2	Q53SZ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRR30	ENST00000335524.7	TSL:1 MANE Select	c.770G>A	p.Arg257Gln	missense	Exon 3 of 3	ENSP00000335017.3	Q53SZ7
	PRR30	ENST00000432962.2	TSL:3	c.276G>A	p.Pro92Pro	synonymous	Exon 4 of 4	ENSP00000393468.2	C9JVA3

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152154 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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

GnomAD2 exomes AF: 0.00000882 AC: 2 AN: 226634 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000555

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000167 AC: 24 AN: 1438008 Hom.: 0 Cov.: 33 AF XY: 0.0000196 AC XY: 14 AN XY: 712506

African (AFR) AF: 0.00 AC: 0 AN: 32990

American (AMR) AF: 0.0000234 AC: 1 AN: 42776

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24366

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39402

South Asian (SAS) AF: 0.0000120 AC: 1 AN: 83180

European-Finnish (FIN) AF: 0.0000196 AC: 1 AN: 51108

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5634

European-Non Finnish (NFE) AF: 0.0000164 AC: 18 AN: 1099386

Other (OTH) AF: 0.0000338 AC: 2 AN: 59166

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152154 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74316

African (AFR) AF: 0.0000483 AC: 2 AN: 41436

American (AMR) AF: 0.0000654 AC: 1 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ESP6500AA AF: 0.000241 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000166 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	6.6
DANN	Benign	0.97
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		-0.33
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.029
Sift	Benign	0.47	T
Sift4G	Benign	0.37	T
Polyphen		0.44	B
Vest4		0.11
MVP		0.25
MPC		0.25
ClinPred		0.060	T
GERP RS		-1.6
Varity_R		0.031
gMVP		0.41
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs377666702; hg19: chr2-27360428;