Variant chr1-27383165-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001330448.1(CD164L2):c.75G>T(p.Gln25His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000134 in 1,548,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

CD164L2
NM_001330448.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.12

Variant links:

Genes affected

CD164L2 (HGNC:32043): (CD164 molecule like 2) Predicted to be integral component of membrane. Predicted to be active in cytoplasmic vesicle. [provided by Alliance of Genome Resources, Apr 2022]

CD164L2 links:

CD164L2 (HGNC:):

CD164L2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3740165).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD164L2	NM_001330448.1 linkuse as main transcript	c.75G>T	p.Gln25His	missense_variant	1/6	ENST00000374030.3	NP_001317377.1	Q6UWJ8-1
CD164L2	NM_207397.5 linkuse as main transcript	c.75G>T	p.Gln25His	missense_variant	1/5		NP_997280.2	Q6UWJ8-2
CD164L2	XM_011541441.2 linkuse as main transcript	c.75G>T	p.Gln25His	missense_variant	1/6		XP_011539743.1	Q6UWJ8-2
CD164L2	XR_241190.4 linkuse as main transcript	n.169G>T		non_coding_transcript_exon_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CD164L2	ENST00000374030.3 linkuse as main transcript	c.75G>T	p.Gln25His	missense_variant	1/6	5	NM_001330448.1	ENSP00000363142.1	Q6UWJ8-1
CD164L2	ENST00000374027.7 linkuse as main transcript	c.75G>T	p.Gln25His	missense_variant	1/5	1		ENSP00000363139.3	Q6UWJ8-2
CD164L2	ENST00000374025.4 linkuse as main transcript	n.142G>T		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152282

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000540

AC:

AN:

148208

Hom.:

AF XY:

0.0000632

AC XY:

AN XY:

79076

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000814

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000110

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000144

AC:

201

AN:

1396328

Hom.:

Cov.:

AF XY:

0.000142

AC XY:

AN XY:

688746

show subpopulations

Gnomad4 AFR exome

AF:

0.0000317

Gnomad4 AMR exome

AF:

0.0000840

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000177

Gnomad4 OTH exome

AF:

0.000104

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152282

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000775

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000134

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 10, 2023

The c.75G>T (p.Q25H) alteration is located in exon 1 (coding exon 1) of the CD164L2 gene. This alteration results from a G to T substitution at nucleotide position 75, causing the glutamine (Q) at amino acid position 25 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.015

.;T

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.75

T;T

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.37

T;T

MetaSVM

Benign

-0.71

MutationAssessor

Uncertain

2.6

M;M

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.74

N;N

REVEL

Uncertain

0.31

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

.;D

Vest4

0.28

MutPred

0.76

Loss of stability (P = 0.0959);Loss of stability (P = 0.0959);

MVP

0.67

MPC

0.53

ClinPred

0.32

GERP RS

3.9

Varity_R

0.077

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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