11-65333844-C-G

Variant names:

• chr11-65333844-C-G
• rs3218610
• ENST00000938273.1:c.-43C>G

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The ENST00000938273.1(DPF2):​c.-43C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0042 in 1,612,820 control chromosomes in the GnomAD database, including 268 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (150 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (118 hom.)
• Consequence: DPF2 ENST00000938273.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.891
• Publications: 3 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 11-65333844-C-G is Benign according to our data. Variant chr11-65333844-C-G is described in ClinVar as Benign. ClinVar VariationId is 1262262.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0753 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000938273.1. 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
	DPF2	NM_006268.5	MANE Select	c.-43C>G		upstream_gene	N/A	NP_006259.1	Q92785-1
	DPF2	NM_001330308.2		c.-43C>G		upstream_gene	N/A	NP_001317237.1	J3KMZ8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPF2	ENST00000938273.1		c.-43C>G		5_prime_UTR	Exon 1 of 11	ENSP00000608332.1
	DPF2	ENST00000703394.1		n.2C>G		non_coding_transcript_exon	Exon 1 of 11
	DPF2	ENST00000528416.6	TSL:1 MANE Select	c.-43C>G		upstream_gene	N/A	ENSP00000436901.1	Q92785-1

Frequencies

GnomAD3 genomes AF: 0.0226 AC: 3438 AN: 152258 Hom.: 152 Cov.: 32

Gnomad AFR AF: 0.0776

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0105

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: 0.000265

Gnomad OTH AF: 0.0205

GnomAD2 exomes AF: 0.00573 AC: 1417 AN: 247140 AF XY: 0.00410

Gnomad AFR exome AF: 0.0758

Gnomad AMR exome AF: 0.00468

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000547

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000108

Gnomad OTH exome AF: 0.00380

GnomAD4 exome AF: 0.00228 AC: 3326 AN: 1460444 Hom.: 118 Cov.: 31 AF XY: 0.00192 AC XY: 1392 AN XY: 726480

African (AFR) AF: 0.0775 AC: 2595 AN: 33466

American (AMR) AF: 0.00502 AC: 224 AN: 44644

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39682

South Asian (SAS) AF: 0.000325 AC: 28 AN: 86180

European-Finnish (FIN) AF: 0.0000190 AC: 1 AN: 52706

Middle Eastern (MID) AF: 0.00209 AC: 12 AN: 5744

European-Non Finnish (NFE) AF: 0.000116 AC: 129 AN: 1111590

Other (OTH) AF: 0.00557 AC: 336 AN: 60334

GnomAD4 genome AF: 0.0226 AC: 3445 AN: 152376 Hom.: 150 Cov.: 32 AF XY: 0.0222 AC XY: 1655 AN XY: 74512

African (AFR) AF: 0.0775 AC: 3223 AN: 41584

American (AMR) AF: 0.0105 AC: 161 AN: 15312

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

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

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68044

Other (OTH) AF: 0.0203 AC: 43 AN: 2116

Alfa AF: 0.00359 Hom.: 4

Bravo AF: 0.0254

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	8.1
DANN	Benign	0.81
PhyloP100		-0.89
PromoterAI		-0.0043	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs3218610; hg19: chr11-65101315;