11-111284321-C-G

Position:

• chr11-111284321-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198498.3(POU2AF2):​c.409C>G​(p.Pro137Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: POU2AF2 NM_198498.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.169

Genes affected

POU2AF2 (HGNC:30527): (POU class 2 homeobox associating factor 2)

ACMG classification

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=0.026105344).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POU2AF2	NM_198498.3	c.409C>G	p.Pro137Ala	missense_variant	4/5	ENST00000280325.7
POU2AF2	XM_011542804.3	c.343C>G	p.Pro115Ala	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POU2AF2	ENST00000280325.7	c.409C>G	p.Pro137Ala	missense_variant	4/5	5	NM_198498.3	P1
POU2AF2	ENST00000637637.1	c.253C>G	p.Pro85Ala	missense_variant	3/4	1
POU2AF2	ENST00000667535.1	n.399C>G		non_coding_transcript_exon_variant	3/4
POU2AF2	ENST00000635886.1	c.*33C>G		3_prime_UTR_variant, NMD_transcript_variant	3/4	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Aug 23, 2021

The c.253C>G (p.P85A) alteration is located in exon 3 (coding exon 2) of the C11orf53 gene. This alteration results from a C to G substitution at nucleotide position 253, causing the proline (P) at amino acid position 85 to be replaced by an alanine (A). 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	0.062
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.051
DANN	Benign	0.27
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.078	N
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.026	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N
REVEL	Benign	0.010
Polyphen		0.0020	.;B
MutPred		0.10		.;Loss of glycosylation at P85 (P = 0.0234);
MVP		0.030
MPC		0.21
ClinPred		0.13	T
GERP RS		-0.83
Varity_R		0.024
gMVP		0.094

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-111155046;