NM_001206927.2:c.11997T>C

Variant names:

• chr6-38938978-T-C
• rs148812133
• NM_001206927.2:c.11997T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001206927.2(DNAH8):​c.11997T>C​(p.Ala3999Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,612,754 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0013 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (11 hom.)
• Consequence: DNAH8 NM_001206927.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.459
• Publications: 3 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 6-38938978-T-C is Benign according to our data. Variant chr6-38938978-T-C is described in ClinVar as Benign. ClinVar VariationId is 414414.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.459 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00132 (201/152276) while in subpopulation AMR AF = 0.00536 (82/15304). AF 95% confidence interval is 0.00442. There are 2 homozygotes in GnomAd4. There are 96 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001206927.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	NM_001206927.2	MANE Select	c.11997T>C	p.Ala3999Ala	synonymous	Exon 79 of 93	NP_001193856.1
	DNAH8	NM_001371.4		c.11346T>C	p.Ala3782Ala	synonymous	Exon 78 of 92	NP_001362.2
	DNAH8-AS1	NR_038401.1		n.61-2586A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	ENST00000327475.11	TSL:5 MANE Select	c.11997T>C	p.Ala3999Ala	synonymous	Exon 79 of 93	ENSP00000333363.7
	DNAH8	ENST00000359357.7	TSL:2	c.11346T>C	p.Ala3782Ala	synonymous	Exon 77 of 91	ENSP00000352312.3
	DNAH8	ENST00000449981.6	TSL:5	c.11997T>C	p.Ala3999Ala	synonymous	Exon 78 of 82	ENSP00000415331.2

Frequencies

GnomAD3 genomes AF: 0.00132 AC: 201 AN: 152158 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00537

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00415

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00118

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00322 AC: 804 AN: 249766 AF XY: 0.00278

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.0162

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000546

Gnomad FIN exome AF: 0.000972

Gnomad NFE exome AF: 0.00111

Gnomad OTH exome AF: 0.000823

GnomAD4 exome AF: 0.00123 AC: 1795 AN: 1460478 Hom.: 11 Cov.: 31 AF XY: 0.00124 AC XY: 899 AN XY: 726542

African (AFR) AF: 0.0000898 AC: 3 AN: 33414

American (AMR) AF: 0.0139 AC: 619 AN: 44434

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26052

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39664

South Asian (SAS) AF: 0.00266 AC: 229 AN: 86030

European-Finnish (FIN) AF: 0.00109 AC: 58 AN: 53380

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5754

European-Non Finnish (NFE) AF: 0.000742 AC: 825 AN: 1111410

Other (OTH) AF: 0.000945 AC: 57 AN: 60340

GnomAD4 genome AF: 0.00132 AC: 201 AN: 152276 Hom.: 2 Cov.: 32 AF XY: 0.00129 AC XY: 96 AN XY: 74454

African (AFR) AF: 0.000193 AC: 8 AN: 41548

American (AMR) AF: 0.00536 AC: 82 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00415 AC: 20 AN: 4818

European-Finnish (FIN) AF: 0.000565 AC: 6 AN: 10614

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00118 AC: 80 AN: 68014

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00102 Hom.: 0

Bravo AF: 0.00190

Asia WGS AF: 0.00202 AC: 7 AN: 3476

EpiCase AF: 0.000274

EpiControl AF: 0.000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DNAH8: BP4, BP7, BS1, BS2

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	7.6
DANN	Benign	0.69
PhyloP100		0.46
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs148812133; hg19: chr6-38906754;