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rs145561539

chr6-38938065-A-Cchr6-38938065-A-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS1

The NM_001206927.2(DNAH8):c.11655A>C(p.Ala3885=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000546 in 1,614,106 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00085 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00052 ( 1 hom. )

Consequence

DNAH8
NM_001206927.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.679
Variant links:
Genes affected
DNAH8 (HGNC:2952): (dynein axonemal heavy chain 8) The protein encoded by this gene is a heavy chain of an axonemal dynein involved in sperm and respiratory cilia motility. Axonemal dyneins generate force through hydrolysis of ATP and binding to microtubules. [provided by RefSeq, Jan 2012]
DNAH8-AS1 (HGNC:40188): (DNAH8 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-38938065-A-C is Benign according to our data. Variant chr6-38938065-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 414433.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.679 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000847 (129/152244) while in subpopulation NFE AF= 0.001 (68/68016). AF 95% confidence interval is 0.000808. There are 0 homozygotes in gnomad4. There are 64 alleles in male gnomad4 subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DNAH8NM_001206927.2 linkuse as main transcriptc.11655A>C p.Ala3885= synonymous_variant 78/93 ENST00000327475.11
DNAH8-AS1NR_038401.1 linkuse as main transcriptn.61-1673T>G intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DNAH8ENST00000327475.11 linkuse as main transcriptc.11655A>C p.Ala3885= synonymous_variant 78/935 NM_001206927.2 P2
DNAH8-AS1ENST00000416948.1 linkuse as main transcriptn.53-1673T>G intron_variant, non_coding_transcript_variant 2
DNAH8ENST00000359357.7 linkuse as main transcriptc.11004A>C p.Ala3668= synonymous_variant 76/912 A2Q96JB1-1
DNAH8ENST00000449981.6 linkuse as main transcriptc.11655A>C p.Ala3885= synonymous_variant 77/825

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000848
AC:
129
AN:
152126
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000966
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000720
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00424
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00100
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000558
AC:
140
AN:
251018
Hom.:
0
AF XY:
0.000523
AC XY:
71
AN XY:
135648
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.0000994
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00356
Gnomad NFE exome
AF:
0.000512
Gnomad OTH exome
AF:
0.000327
GnomAD4 exome
AF:
0.000515
AC:
753
AN:
1461862
Hom.:
1
Cov.:
33
AF XY:
0.000491
AC XY:
357
AN XY:
727230
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000894
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00399
Gnomad4 NFE exome
AF:
0.000458
Gnomad4 OTH exome
AF:
0.000414
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000847
AC:
129
AN:
152244
Hom.:
0
Cov.:
31
AF XY:
0.000860
AC XY:
64
AN XY:
74440
show subpopulations
Gnomad4 AFR
AF:
0.0000963
Gnomad4 AMR
AF:
0.000719
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00424
Gnomad4 NFE
AF:
0.00100
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000853
Hom.:
0
Bravo
AF:
0.000355
EpiCase
AF:
0.000218
EpiControl
AF:
0.000356

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Primary ciliary dyskinesia Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeJan 12, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.55
Cadd
Benign
1.6
Dann
Benign
0.70

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs145561539; hg19: chr6-38905841; API