rs6450512

Variant names:

• chr5-59215675-G-A
• rs6450512
• NM_001104631.2:c.647+102C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-59215675-G-A
• chr5-59215675-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001104631.2(PDE4D):​c.647+102C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 931,594 control chromosomes in the GnomAD database, including 91,558 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (22124 hom., cov: 31)
  • Exomes 𝑓: 0.41 (69434 hom.)
• Consequence: PDE4D NM_001104631.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0400
• Publications: 11 publications found

Genes affected

PDE4D (HGNC:8783): (phosphodiesterase 4D) This gene encodes one of four mammalian counterparts to the fruit fly 'dunce' gene. The encoded protein has 3',5'-cyclic-AMP phosphodiesterase activity and degrades cAMP, which acts as a signal transduction molecule in multiple cell types. This gene uses different promoters to generate multiple alternatively spliced transcript variants that encode functional proteins.[provided by RefSeq, Sep 2009]

PDE4D Gene-Disease associations (from GenCC):

• acrodysostosis 2 with or without hormone resistance

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• acrodysostosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• acrodysostosis with multiple hormone resistance

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• chromosome 5q12 deletion syndrome

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 5-59215675-G-A is Benign according to our data. Variant chr5-59215675-G-A is described in ClinVar as [Benign]. Clinvar id is 1241786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4D	NM_001104631.2	c.647+102C>T		intron_variant	Intron 2 of 14	ENST00000340635.11	NP_001098101.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE4D	ENST00000340635.11	c.647+102C>T		intron_variant	Intron 2 of 14	1	NM_001104631.2	ENSP00000345502.6

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76621 AN: 151674 Hom.: 22063 Cov.: 31

Gnomad AFR AF: 0.790

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.457

GnomAD4 exome AF: 0.410 AC: 319724 AN: 779802 Hom.: 69434 Cov.: 10 AF XY: 0.412 AC XY: 168354 AN XY: 408434

African (AFR) AF: 0.797 AC: 15580 AN: 19540

American (AMR) AF: 0.436 AC: 15191 AN: 34804

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 5629 AN: 19008

East Asian (EAS) AF: 0.551 AC: 19924 AN: 36156

South Asian (SAS) AF: 0.556 AC: 35176 AN: 63282

European-Finnish (FIN) AF: 0.405 AC: 19468 AN: 48114

Middle Eastern (MID) AF: 0.359 AC: 1296 AN: 3608

European-Non Finnish (NFE) AF: 0.370 AC: 191828 AN: 517876

Other (OTH) AF: 0.418 AC: 15632 AN: 37414

GnomAD4 genome AF: 0.506 AC: 76737 AN: 151792 Hom.: 22124 Cov.: 31 AF XY: 0.505 AC XY: 37434 AN XY: 74166

African (AFR) AF: 0.790 AC: 32717 AN: 41388

American (AMR) AF: 0.442 AC: 6725 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 1082 AN: 3466

East Asian (EAS) AF: 0.564 AC: 2909 AN: 5154

South Asian (SAS) AF: 0.572 AC: 2756 AN: 4820

European-Finnish (FIN) AF: 0.413 AC: 4343 AN: 10510

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.364 AC: 24750 AN: 67920

Other (OTH) AF: 0.462 AC: 972 AN: 2106

Alfa AF: 0.394 Hom.: 24682

Bravo AF: 0.519

Asia WGS AF: 0.635 AC: 2208 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.74
DANN	Benign	0.38
PhyloP100		-0.040
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: rs6450512; hg19: chr5-58511501; COSMIC: COSV58940168;