5-93741026-G-C

Variant names:

• chr5-93741026-G-C
• rs200489758
• NM_153216.2:c.538C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_153216.2(POU5F2):​c.538C>G​(p.Leu180Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000212 in 1,461,570 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: 0.000021 (0 hom.)
• Consequence: POU5F2 NM_153216.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.95
• Publications: 2 publications found

Genes affected

POU5F2 (HGNC:26367): (POU domain class 5, transcription factor 2) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ARB2A (HGNC:25365): (ARB2 cotranscriptional regulator A) Predicted to contribute to siRNA binding activity. Predicted to be involved in heterochromatin assembly by small RNA; neural crest cell development; and regulation of alternative mRNA splicing, via spliceosome. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153216.2. 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
	POU5F2	NM_153216.2	MANE Select	c.538C>G	p.Leu180Val	missense	Exon 1 of 1	NP_694948.1	Q8N7G0
	ARB2A	NM_032042.6	MANE Select	c.1108+35133C>G		intron	N/A	NP_114431.2
	ARB2A	NM_001163417.1		c.970+35133C>G		intron	N/A	NP_001156889.1	Q8WUF8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU5F2	ENST00000606183.4	TSL:6 MANE Select	c.538C>G	p.Leu180Val	missense	Exon 1 of 1	ENSP00000489796.1	Q8N7G0
	ARB2A	ENST00000395965.8	TSL:1 MANE Select	c.1108+35133C>G		intron	N/A	ENSP00000379294.3	Q8WUF8-1
	ARB2A	ENST00000881906.1		c.1144+2511C>G		intron	N/A	ENSP00000551965.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000201 AC: 5 AN: 249144 AF XY: 0.00000740

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000354

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.0000212 AC: 31 AN: 1461570 Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18 AN XY: 727076

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53230

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000270 AC: 30 AN: 1111904

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000694 Hom.: 0

Bravo AF: 0.0000340

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000234 AC: 2

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	20
DANN	Benign	0.46
DEOGEN2	Pathogenic	0.80	D
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.096	D
MetaRNN	Uncertain	0.64	D
MutationAssessor	Benign	1.5	L
PhyloP100		3.9
PrimateAI	Benign	0.37	T
Polyphen		0.96	D
GERP RS		1.1
Varity_R		0.069
gMVP		0.79
Mutation Taster		=59/41	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs200489758; hg19: chr5-93076732;