5-160092729-T-G

Position:

• chr5-160092729-T-G

Variant summary

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

The NM_001130864.2(PWWP2A):​c.1921A>C​(p.Asn641His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PWWP2A NM_001130864.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.17

Genes affected

PWWP2A (HGNC:29406): (PWWP domain containing 2A) Enables chromatin binding activity and histone binding activity. Located in nucleus. [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=0.23511744).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PWWP2A	NM_001130864.2	c.1921A>C	p.Asn641His	missense_variant	2/2	ENST00000307063.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PWWP2A	ENST00000307063.9	c.1921A>C	p.Asn641His	missense_variant	2/2	1	NM_001130864.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1399080 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 690038

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Jan 23, 2023

The c.1921A>C (p.N641H) alteration is located in exon 2 (coding exon 2) of the PWWP2A gene. This alteration results from a A to C substitution at nucleotide position 1921, causing the asparagine (N) at amino acid position 641 to be replaced by a histidine (H). 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	0.33
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.083	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.2	L
MutationTaster	Benign	0.92	D;D;D
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.15
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.089	T
Polyphen		0.98	D
Vest4		0.24
MutPred		0.33		Loss of sheet (P = 0.0104);
MVP		0.10
MPC		1.7
ClinPred		0.81	D
GERP RS		5.8
Varity_R		0.17
gMVP		0.60

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: chr5-159519736;