rs41269807

Variant names:

• chr1-13780865-T-A
• rs41269807
• NM_001393986.1:c.3070T>A

Your query was ambiguous. Multiple possible variants found:

• chr1-13780865-T-A
• chr1-13780865-T-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001393986.1(PRDM2):​c.3070T>A​(p.Ser1024Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0413 in 1,610,400 control chromosomes in the GnomAD database, including 1,547 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.031 (116 hom., cov: 30)
  • Exomes 𝑓: 0.042 (1431 hom.)
• Consequence: PRDM2 NM_001393986.1 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 6.47
• Publications: 9 publications found

Genes affected

PRDM2 (HGNC:9347): (PR/SET domain 2) This tumor suppressor gene is a member of a nuclear histone/protein methyltransferase superfamily. It encodes a zinc finger protein that can bind to retinoblastoma protein, estrogen receptor, and the TPA-responsive element (MTE) of the heme-oxygenase-1 gene. Although the functions of this protein have not been fully characterized, it may (1) play a role in transcriptional regulation during neuronal differentiation and pathogenesis of retinoblastoma, (2) act as a transcriptional activator of the heme-oxygenase-1 gene, and (3) be a specific effector of estrogen action. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00453192).
• BP6: Variant 1-13780865-T-A is Benign according to our data. Variant chr1-13780865-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 403342.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0312 (4710/150756) while in subpopulation NFE AF = 0.0467 (3166/67732). AF 95% confidence interval is 0.0454. There are 116 homozygotes in GnomAd4. There are 2255 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4710 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393986.1. 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
	PRDM2	NM_001393986.1	MANE Select	c.3070T>A	p.Ser1024Thr	missense	Exon 8 of 10	NP_001380915.1	Q13029-1
	PRDM2	NM_012231.5		c.3070T>A	p.Ser1024Thr	missense	Exon 8 of 10	NP_036363.2
	PRDM2	NM_015866.6		c.3070T>A	p.Ser1024Thr	missense	Exon 8 of 9	NP_056950.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM2	ENST00000311066.10	TSL:5 MANE Select	c.3070T>A	p.Ser1024Thr	missense	Exon 8 of 10	ENSP00000312352.6	Q13029-1
	PRDM2	ENST00000235372.11	TSL:1	c.3070T>A	p.Ser1024Thr	missense	Exon 8 of 10	ENSP00000235372.6	Q13029-1
	PRDM2	ENST00000343137.8	TSL:1	c.2467T>A	p.Ser823Thr	missense	Exon 4 of 5	ENSP00000341621.4	Q13029-5

Frequencies

GnomAD3 genomes AF: 0.0313 AC: 4708 AN: 150640 Hom.: 116 Cov.: 30

Gnomad AFR AF: 0.00847

Gnomad AMI AF: 0.00549

Gnomad AMR AF: 0.0348

Gnomad ASJ AF: 0.0470

Gnomad EAS AF: 0.000588

Gnomad SAS AF: 0.0360

Gnomad FIN AF: 0.0241

Gnomad MID AF: 0.0224

Gnomad NFE AF: 0.0468

Gnomad OTH AF: 0.0336

GnomAD2 exomes AF: 0.0346 AC: 8686 AN: 251014 AF XY: 0.0366

Gnomad AFR exome AF: 0.00744

Gnomad AMR exome AF: 0.0225

Gnomad ASJ exome AF: 0.0461

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0266

Gnomad NFE exome AF: 0.0470

Gnomad OTH exome AF: 0.0403

GnomAD4 exome AF: 0.0423 AC: 61765 AN: 1459644 Hom.: 1431 Cov.: 53 AF XY: 0.0421 AC XY: 30559 AN XY: 726252

African (AFR) AF: 0.00703 AC: 235 AN: 33438

American (AMR) AF: 0.0232 AC: 1038 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.0445 AC: 1163 AN: 26110

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39692

South Asian (SAS) AF: 0.0394 AC: 3397 AN: 86164

European-Finnish (FIN) AF: 0.0274 AC: 1466 AN: 53412

Middle Eastern (MID) AF: 0.0475 AC: 274 AN: 5764

European-Non Finnish (NFE) AF: 0.0466 AC: 51783 AN: 1110076

Other (OTH) AF: 0.0399 AC: 2405 AN: 60282

GnomAD4 genome AF: 0.0312 AC: 4710 AN: 150756 Hom.: 116 Cov.: 30 AF XY: 0.0307 AC XY: 2255 AN XY: 73570

African (AFR) AF: 0.00845 AC: 346 AN: 40956

American (AMR) AF: 0.0348 AC: 527 AN: 15146

Ashkenazi Jewish (ASJ) AF: 0.0470 AC: 163 AN: 3466

East Asian (EAS) AF: 0.000590 AC: 3 AN: 5086

South Asian (SAS) AF: 0.0365 AC: 172 AN: 4712

European-Finnish (FIN) AF: 0.0241 AC: 250 AN: 10352

Middle Eastern (MID) AF: 0.0276 AC: 8 AN: 290

European-Non Finnish (NFE) AF: 0.0467 AC: 3166 AN: 67732

Other (OTH) AF: 0.0332 AC: 70 AN: 2106

Alfa AF: 0.0434 Hom.: 127

Bravo AF: 0.0303

TwinsUK AF: 0.0520 AC: 193

ALSPAC AF: 0.0402 AC: 155

ESP6500AA AF: 0.00749 AC: 33

ESP6500EA AF: 0.0451 AC: 388

ExAC AF: 0.0351 AC: 4258

Asia WGS AF: 0.0140 AC: 50 AN: 3478

EpiCase AF: 0.0486

EpiControl AF: 0.0470

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	23
DANN	Benign	0.95
DEOGEN2	Benign	0.084	T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.85	D
MetaRNN	Benign	0.0045	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		6.5
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.17
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.089	T
Polyphen		0.86	P
Vest4		0.24
MPC		0.17
ClinPred		0.033	T
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.47
Mutation Taster		=94/6	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: rs41269807; hg19: chr1-14107360; COSMIC: COSV52446694; COSMIC: COSV52446694;