7-6466270-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_006854.4(KDELR2):c.405A>G(p.Leu135Leu) 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 (★). Synonymous variant affecting the same amino acid position (i.e. L135L) has been classified as Uncertain significance.

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

Publications

22 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 1278607.Status of the report is criteria_provided_single_submitter, 1 stars.

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006854.4. 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
	KDELR2	NM_006854.4	MANE Select	c.405A>G	p.Leu135Leu	synonymous	Exon 4 of 5	NP_006845.1	P33947-1
	KDELR2	NM_001100603.2		c.352-3095A>G		intron	N/A	NP_001094073.1	P33947-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KDELR2	ENST00000258739.9	TSL:1 MANE Select	c.405A>G	p.Leu135Leu	synonymous	Exon 4 of 5	ENSP00000258739.4	P33947-1
KDELR2	ENST00000490996.1	TSL:1	c.352-3095A>G		intron	N/A	ENSP00000420501.1	P33947-2
KDELR2	ENST00000854603.1		c.522A>G	p.Leu174Leu	synonymous	Exon 5 of 6	ENSP00000524662.1

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

GnomAD2 exomes

AF:

0.874

AC:

219858

AN:

251478

AF XY:

0.868

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 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

African (AFR)

AF:

0.976

AC:

32684

AN:

33480

American (AMR)

AF:

0.864

AC:

38658

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.930

AC:

24309

AN:

26136

East Asian (EAS)

AF:

0.572

AC:

22723

AN:

39698

South Asian (SAS)

AF:

0.710

AC:

61227

AN:

86254

European-Finnish (FIN)

AF:

0.960

AC:

51298

AN:

53418

Middle Eastern (MID)

AF:

0.874

AC:

5035

AN:

5760

European-Non Finnish (NFE)

AF:

0.936

AC:

1040517

AN:

1111996

Other (OTH)

AF:

0.898

AC:

54248

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

6542

13084

19626

26168

32710

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21494

42988

64482

85976

107470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.922

AC:

140271

AN:

152198

Hom.:

65227

Cov.:

AF XY:

0.917

AC XY:

68199

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.973

AC:

40406

AN:

41522

American (AMR)

AF:

0.879

AC:

13432

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.933

AC:

3239

AN:

3472

East Asian (EAS)

AF:

0.577

AC:

2983

AN:

5174

South Asian (SAS)

AF:

0.698

AC:

3365

AN:

4824

European-Finnish (FIN)

AF:

0.962

AC:

10202

AN:

10606

Middle Eastern (MID)

AF:

0.861

AC:

253

AN:

294

European-Non Finnish (NFE)

AF:

0.935

AC:

63578

AN:

68002

Other (OTH)

AF:

0.916

AC:

1935

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

497

994

1491

1988

2485

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

898

1796

2694

3592

4490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.929

Hom.:

46541

Bravo

AF:

0.922

Asia WGS

AF:

0.628

AC:

2187

AN:

3478

EpiCase

AF:

0.930

EpiControl

AF:

0.932

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

7.9

(source)

DANN

Benign

0.77

PhyloP100

-0.52

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over