11-111306615-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001271458.2(POU2AF3):c.379C>A(p.Gln127Lys) 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: POU2AF3 NM_001271458.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.20

Genes affected

POU2AF3 (HGNC:26978): (POU class 2 homeobox associating factor 3) Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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=0.23266685).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POU2AF3	NM_001271458.2	c.379C>A	p.Gln127Lys	missense_variant	4/5	ENST00000610738.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POU2AF3	ENST00000610738.6	c.379C>A	p.Gln127Lys	missense_variant	4/5	1	NM_001271458.2	P2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

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

Nov 18, 2023

The c.88C>A (p.Q30K) alteration is located in exon 4 (coding exon 1) of the COLCA2 gene. This alteration results from a C to A substitution at nucleotide position 88, causing the glutamine (Q) at amino acid position 30 to be replaced by a lysine (K). 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	0.15
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
Cadd	Benign	20
Dann	Benign	0.96
Eigen	Benign	-0.064
Eigen_PC	Benign	0.059
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.78	T;T;T;T;.;.
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.23	T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	0.81	N;N
Sift4G	Benign	0.17	T;.;D;D;D;D
Polyphen		0.57	.;.;.;P;P;P
Vest4		0.52
MutPred		0.21		.;.;Gain of methylation at Q30 (P = 0.0037);Gain of methylation at Q30 (P = 0.0037);Gain of methylation at Q30 (P = 0.0037);Gain of methylation at Q30 (P = 0.0037);
MVP		0.085
ClinPred		0.75	D
GERP RS		4.9
Varity_R		0.34
gMVP		0.16

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: chr11-111177340;