chr21-41800831-G-C

Variant names:

• chr21-41800831-G-C
• rs2236693
• ENST00000441787.5:n.*2286C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000441787.5(PRDM15):​n.*2286C>G variant causes a non coding transcript exon 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRDM15 ENST00000441787.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.519
• Publications: 5 publications found

Genes affected

PRDM15 (HGNC:13999): (PR/SET domain 15) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and promoter-specific chromatin binding activity. Predicted to be involved in positive regulation of transcription by RNA polymerase II; regulation of signal transduction; and regulation of stem cell division. Located in nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM15	NM_001040424.3	c.*409C>G		3_prime_UTR_variant	Exon 24 of 24	ENST00000398548.6	NP_001035514.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM15	ENST00000398548.6	c.*409C>G		3_prime_UTR_variant	Exon 24 of 24	1	NM_001040424.3	ENSP00000381556.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 13626 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6778

African (AFR) AF: 0.00 AC: 0 AN: 564

American (AMR) AF: 0.00 AC: 0 AN: 590

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 494

East Asian (EAS) AF: 0.00 AC: 0 AN: 532

South Asian (SAS) AF: 0.00 AC: 0 AN: 210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 72

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 9740

Other (OTH) AF: 0.00 AC: 0 AN: 864

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.41
DANN	Benign	0.44
PhyloP100		-0.52

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2236693; hg19: chr21-43220991;