rs2945999

Variant names:

• chr11-45961406-T-G
• rs2945999
• NM_001352027.3:c.996+3909A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001352027.3(PHF21A):​c.996+3909A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 152,064 control chromosomes in the GnomAD database, including 22,522 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (22522 hom., cov: 32)
• Consequence: PHF21A NM_001352027.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• Publications: 3 publications found

Genes affected

PHF21A (HGNC:24156): (PHD finger protein 21A) The PHF21A gene encodes BHC80, a component of a BRAF35 (MIM 605535)/histone deacetylase (HDAC; see MIM 601241) complex (BHC) that mediates repression of neuron-specific genes through the cis-regulatory element known as repressor element-1 (RE1) or neural restrictive silencer (NRS) (Hakimi et al., 2002 [PubMed 12032298]).[supplied by OMIM, Nov 2010]

PHF21A Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Potocki-Shaffer syndrome

  Inheritance: AD Classification: STRONG Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF21A	NM_001352027.3	c.996+3909A>C		intron_variant	Intron 10 of 18	ENST00000676320.1	NP_001338956.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF21A	ENST00000676320.1	c.996+3909A>C		intron_variant	Intron 10 of 18		NM_001352027.3	ENSP00000502222.1

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77115 AN: 151944 Hom.: 22523 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.736

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.556

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.507 AC: 77119 AN: 152064 Hom.: 22522 Cov.: 32 AF XY: 0.507 AC XY: 37669 AN XY: 74330

African (AFR) AF: 0.229 AC: 9511 AN: 41492

American (AMR) AF: 0.531 AC: 8116 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.736 AC: 2551 AN: 3468

East Asian (EAS) AF: 0.173 AC: 899 AN: 5182

South Asian (SAS) AF: 0.566 AC: 2730 AN: 4820

European-Finnish (FIN) AF: 0.628 AC: 6619 AN: 10536

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.659 AC: 44757 AN: 67964

Other (OTH) AF: 0.561 AC: 1183 AN: 2110

Alfa AF: 0.594 Hom.: 6693

Bravo AF: 0.484

Asia WGS AF: 0.376 AC: 1313 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.7
DANN	Benign	0.64
PhyloP100		0.055
Mutation Taster		=100/0	polymorphism (auto)

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: rs2945999; hg19: chr11-45982957;