Variant 7-6466270-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_006854.4(KDELR2):c.405A>G(p.Leu135=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.911 in 1,614,058 control chromosomes in the GnomAD database, including 676,066 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.92 ( 65227 hom., cov: 30)

Exomes 𝑓: 0.91 ( 610839 hom. )

Consequence

KDELR2
NM_006854.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.523

Variant links:

Genes affected

KDELR2 (HGNC:6305): (KDEL endoplasmic reticulum protein retention receptor 2) Retention of resident soluble proteins in the lumen of the endoplasmic reticulum (ER) is achieved in both yeast and animal cells by their continual retrieval from the cis-Golgi, or a pre-Golgi compartment. Sorting of these proteins is dependent on a C-terminal tetrapeptide signal, usually lys-asp-glu-leu (KDEL) in animal cells, and his-asp-glu-leu (HDEL) in S. cerevisiae. This process is mediated by a receptor that recognizes, and binds the tetrapeptide-containing protein, and returns it to the ER. In yeast, the sorting receptor encoded by a single gene, ERD2, is a seven-transmembrane protein. Unlike yeast, several human homologs of the ERD2 gene, constituting the KDEL receptor gene family, have been described. KDELR2 was the second member of the family to be identified, and it encodes a protein which is 83% identical to the KDELR1 gene product. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

KDELR2 links:

DAGLB (HGNC:28923): (diacylglycerol lipase beta) Enables lipase activity. Involved in arachidonic acid metabolic process. Located in nucleoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

DAGLB links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 7-6466270-T-C is Benign according to our data. Variant chr7-6466270-T-C is described in ClinVar as [Benign]. Clinvar id is 1278607.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-6466270-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.523 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDELR2	NM_006854.4 linkuse as main transcript	c.405A>G	p.Leu135=	synonymous_variant	4/5	ENST00000258739.9	NP_006845.1
KDELR2	NM_001100603.2 linkuse as main transcript	c.352-3095A>G		intron_variant			NP_001094073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDELR2	ENST00000258739.9 linkuse as main transcript	c.405A>G	p.Leu135=	synonymous_variant	4/5	1	NM_006854.4	ENSP00000258739	P1	P33947-1

Frequencies

GnomAD3 genomes

AF:

0.922

AC:

140168

AN:

152080

Hom.:

65178

Cov.:

show subpopulations

Gnomad AFR

AF:

0.973

Gnomad AMI

AF:

0.963

Gnomad AMR

AF:

0.879

Gnomad ASJ

AF:

0.933

Gnomad EAS

AF:

0.577

Gnomad SAS

AF:

0.696

Gnomad FIN

AF:

0.962

Gnomad MID

AF:

0.870

Gnomad NFE

AF:

0.935

Gnomad OTH

AF:

0.923

GnomAD3 exomes

AF:

0.874

AC:

219858

AN:

251478

Hom.:

97881

AF XY:

0.868

AC XY:

117952

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.976

Gnomad AMR exome

AF:

0.861

Gnomad ASJ exome

AF:

0.926

Gnomad EAS exome

AF:

0.585

Gnomad SAS exome

AF:

0.703

Gnomad FIN exome

AF:

0.958

Gnomad NFE exome

AF:

0.935

Gnomad OTH exome

AF:

0.900

GnomAD4 exome

AF:

0.910

AC:

1330699

AN:

1461860

Hom.:

610839

Cov.:

AF XY:

0.904

AC XY:

657591

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.976

Gnomad4 AMR exome

AF:

0.864

Gnomad4 ASJ exome

AF:

0.930

Gnomad4 EAS exome

AF:

0.572

Gnomad4 SAS exome

AF:

0.710

Gnomad4 FIN exome

AF:

0.960

Gnomad4 NFE exome

AF:

0.936

Gnomad4 OTH exome

AF:

0.898

GnomAD4 genome

AF:

0.922

AC:

140271

AN:

152198

Hom.:

65227

Cov.:

AF XY:

0.917

AC XY:

68199

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.973

Gnomad4 AMR

AF:

0.879

Gnomad4 ASJ

AF:

0.933

Gnomad4 EAS

AF:

0.577

Gnomad4 SAS

AF:

0.698

Gnomad4 FIN

AF:

0.962

Gnomad4 NFE

AF:

0.935

Gnomad4 OTH

AF:

0.916

Alfa

AF:

0.929

Hom.:

41533

Bravo

AF:

0.922

Asia WGS

AF:

0.628

AC:

2187

AN:

3478

EpiCase

AF:

0.930

EpiControl

AF:

0.932

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

7.9

DANN

Benign

0.77

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over