chr14-54962541-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_007086.4(WDHD1):​c.2658G>A​(p.Ser886=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000183 in 1,609,584 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 Benign (★).

Frequency

Genomes: 𝑓 0.00074 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

WDHD1
NM_007086.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.33
Variant links:
Genes affected
WDHD1 (HGNC:23170): (WD repeat and HMG-box DNA binding protein 1) The protein encoded by this gene contains multiple N-terminal WD40 domains and a C-terminal high mobility group (HMG) box. WD40 domains are found in a variety of eukaryotic proteins and may function as adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly. HMG boxes are found in many eukaryotic proteins involved in chromatin assembly, transcription and replication. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant 14-54962541-C-T is Benign according to our data. Variant chr14-54962541-C-T is described in ClinVar as [Benign]. Clinvar id is 712596.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.34 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
WDHD1NM_007086.4 linkuse as main transcriptc.2658G>A p.Ser886= synonymous_variant 21/26 ENST00000360586.8 NP_009017.1
WDHD1NM_001008396.3 linkuse as main transcriptc.2289G>A p.Ser763= synonymous_variant 20/25 NP_001008397.1
WDHD1XM_006720012.2 linkuse as main transcriptc.2658G>A p.Ser886= synonymous_variant 21/26 XP_006720075.1
WDHD1XM_011536373.3 linkuse as main transcriptc.1569G>A p.Ser523= synonymous_variant 12/17 XP_011534675.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
WDHD1ENST00000360586.8 linkuse as main transcriptc.2658G>A p.Ser886= synonymous_variant 21/261 NM_007086.4 ENSP00000353793 P1O75717-1
WDHD1ENST00000420358.2 linkuse as main transcriptc.2289G>A p.Ser763= synonymous_variant 20/255 ENSP00000399349 O75717-2
WDHD1ENST00000567693.1 linkuse as main transcriptc.*1108G>A 3_prime_UTR_variant, NMD_transcript_variant 9/142 ENSP00000456806

Frequencies

GnomAD3 genomes
AF:
0.000730
AC:
111
AN:
152114
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00191
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00210
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000465
AC:
116
AN:
249392
Hom.:
0
AF XY:
0.000378
AC XY:
51
AN XY:
134918
show subpopulations
Gnomad AFR exome
AF:
0.00174
Gnomad AMR exome
AF:
0.00250
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000331
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000126
AC:
183
AN:
1457352
Hom.:
0
Cov.:
30
AF XY:
0.000110
AC XY:
80
AN XY:
725268
show subpopulations
Gnomad4 AFR exome
AF:
0.00174
Gnomad4 AMR exome
AF:
0.00238
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000117
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000126
Gnomad4 OTH exome
AF:
0.0000664
GnomAD4 genome
AF:
0.000736
AC:
112
AN:
152232
Hom.:
0
Cov.:
32
AF XY:
0.000806
AC XY:
60
AN XY:
74416
show subpopulations
Gnomad4 AFR
AF:
0.00193
Gnomad4 AMR
AF:
0.00209
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000329
Hom.:
0
Bravo
AF:
0.000782
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJul 04, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
0.84
DANN
Benign
0.25
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.15
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.

Other links and lift over

dbSNP: rs142576091; hg19: chr14-55429259; API