rs2236518

Variant names:

• chr1-3436308-A-C
• rs2236518
• NM_022114.4:c.*2497A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-3436308-A-C
• chr1-3436308-A-G

Variant summary

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

The NM_022114.4(PRDM16):​c.*2497A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 230,388 control chromosomes in the GnomAD database, including 17,406 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 0.38 (12982 hom., cov: 31)
  • Exomes 𝑓: 0.32 (4424 hom.)
• Consequence: PRDM16 NM_022114.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.49
• Publications: 16 publications found

Genes affected

PRDM16 (HGNC:14000): (PR/SET domain 16) The reciprocal translocation t(1;3)(p36;q21) occurs in a subset of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). This gene is located near the 1p36.3 breakpoint and has been shown to be specifically expressed in the t(1:3)(p36,q21)-positive MDS/AML. The protein encoded by this gene is a zinc finger transcription factor and contains an N-terminal PR domain. The translocation results in the overexpression of a truncated version of this protein that lacks the PR domain, which may play an important role in the pathogenesis of MDS and AML. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

PRDM16 Gene-Disease associations (from GenCC):

• left ventricular noncompaction 8

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae)
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• left ventricular noncompaction

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• dilated cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022114.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM16	NM_022114.4	MANE Select	c.*2497A>C		3_prime_UTR	Exon 17 of 17	NP_071397.3
	PRDM16	NM_199454.3		c.*2497A>C		3_prime_UTR	Exon 17 of 17	NP_955533.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM16	ENST00000270722.10	TSL:1 MANE Select	c.*2497A>C		3_prime_UTR	Exon 17 of 17	ENSP00000270722.5

Frequencies

GnomAD3 genomes AF: 0.383 AC: 57889 AN: 151324 Hom.: 12949 Cov.: 31

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.356

GnomAD4 exome AF: 0.316 AC: 24921 AN: 78944 Hom.: 4424 Cov.: 0 AF XY: 0.309 AC XY: 11218 AN XY: 36326

African (AFR) AF: 0.620 AC: 2345 AN: 3784

American (AMR) AF: 0.370 AC: 899 AN: 2428

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 1212 AN: 4984

East Asian (EAS) AF: 0.501 AC: 5610 AN: 11188

South Asian (SAS) AF: 0.319 AC: 221 AN: 692

European-Finnish (FIN) AF: 0.243 AC: 17 AN: 70

Middle Eastern (MID) AF: 0.293 AC: 140 AN: 478

European-Non Finnish (NFE) AF: 0.254 AC: 12396 AN: 48726

Other (OTH) AF: 0.316 AC: 2081 AN: 6594

GnomAD4 genome AF: 0.383 AC: 57974 AN: 151444 Hom.: 12982 Cov.: 31 AF XY: 0.383 AC XY: 28288 AN XY: 73930

African (AFR) AF: 0.622 AC: 25670 AN: 41288

American (AMR) AF: 0.365 AC: 5566 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 845 AN: 3462

East Asian (EAS) AF: 0.558 AC: 2856 AN: 5120

South Asian (SAS) AF: 0.327 AC: 1561 AN: 4778

European-Finnish (FIN) AF: 0.244 AC: 2548 AN: 10436

Middle Eastern (MID) AF: 0.318 AC: 93 AN: 292

European-Non Finnish (NFE) AF: 0.262 AC: 17775 AN: 67814

Other (OTH) AF: 0.358 AC: 754 AN: 2108

Alfa AF: 0.291 Hom.: 8987

Bravo AF: 0.402

Asia WGS AF: 0.463 AC: 1610 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.51
DANN	Benign	0.44
PhyloP100		-3.5
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: rs2236518; hg19: chr1-3352872; COSMIC: COSV54585038; COSMIC: COSV54585038;