chr11-65340442-C-T

Variant names:

• chr11-65340442-C-T
• rs4647578
• NM_006268.5:c.90C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_006268.5(DPF2):​c.90C>T​(p.Arg30Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00205 in 1,614,250 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (32 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (31 hom.)
• Consequence: DPF2 NM_006268.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.822
• Publications: 1 publications found

Genes affected

DPF2 (HGNC:9964): (double PHD fingers 2) The protein encoded by this gene is a member of the d4 domain family, characterized by a zinc finger-like structural motif. This protein functions as a transcription factor which is necessary for the apoptotic response following deprivation of survival factors. It likely serves a regulatory role in rapid hematopoietic cell growth and turnover. This gene is considered a candidate gene for multiple endocrine neoplasia type I, an inherited cancer syndrome involving multiple parathyroid, enteropancreatic, and pituitary tumors. [provided by RefSeq, Jul 2008]

DPF2 Gene-Disease associations (from GenCC):

• Coffin-Siris syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Coffin-Siris syndrome 7

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

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP6: Variant 11-65340442-C-T is Benign according to our data. Variant chr11-65340442-C-T is described in ClinVar as Benign. ClinVar VariationId is 1589308.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.822 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0107 (1627/152358) while in subpopulation AFR AF = 0.0374 (1555/41578). AF 95% confidence interval is 0.0359. There are 32 homozygotes in GnomAd4. There are 796 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1627 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006268.5. 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
	DPF2	NM_006268.5	MANE Select	c.90C>T	p.Arg30Arg	synonymous	Exon 2 of 11	NP_006259.1	Q92785-1
	DPF2	NM_001330308.2		c.90C>T	p.Arg30Arg	synonymous	Exon 2 of 12	NP_001317237.1	J3KMZ8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPF2	ENST00000528416.6	TSL:1 MANE Select	c.90C>T	p.Arg30Arg	synonymous	Exon 2 of 11	ENSP00000436901.1	Q92785-1
	DPF2	ENST00000703424.1		c.90C>T	p.Arg30Arg	synonymous	Exon 2 of 11	ENSP00000515295.1	A0A994J6A8
	DPF2	ENST00000703425.1		c.159C>T	p.Arg53Arg	synonymous	Exon 3 of 13	ENSP00000515296.1	A0A994J426

Frequencies

GnomAD3 genomes AF: 0.0107 AC: 1626 AN: 152240 Hom.: 32 Cov.: 32

Gnomad AFR AF: 0.0375

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00716

GnomAD2 exomes AF: 0.00258 AC: 649 AN: 251416 AF XY: 0.00187

Gnomad AFR exome AF: 0.0360

Gnomad AMR exome AF: 0.00119

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000114

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00115 AC: 1685 AN: 1461892 Hom.: 31 Cov.: 31 AF XY: 0.000978 AC XY: 711 AN XY: 727246

African (AFR) AF: 0.0397 AC: 1328 AN: 33480

American (AMR) AF: 0.00143 AC: 64 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.000110 AC: 122 AN: 1112010

Other (OTH) AF: 0.00267 AC: 161 AN: 60396

GnomAD4 genome AF: 0.0107 AC: 1627 AN: 152358 Hom.: 32 Cov.: 32 AF XY: 0.0107 AC XY: 796 AN XY: 74498

African (AFR) AF: 0.0374 AC: 1555 AN: 41578

American (AMR) AF: 0.00301 AC: 46 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68034

Other (OTH) AF: 0.00709 AC: 15 AN: 2116

Alfa AF: 0.00557 Hom.: 6

Bravo AF: 0.0124

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	DPF2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	12
DANN	Benign	0.62
PhyloP100		0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4647578; hg19: chr11-65107913;