chr6-38915224-C-T

Variant names:

• chr6-38915224-C-T
• rs150857304
• NM_001206927.2:c.9987C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001206927.2(DNAH8):​c.9987C>T​(p.Ser3329Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00267 in 1,604,264 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 Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0022 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (13 hom.)
• Consequence: DNAH8 NM_001206927.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.352
• Publications: 2 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 6-38915224-C-T is Benign according to our data. Variant chr6-38915224-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 414400.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.352 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00225 (342/152208) while in subpopulation NFE AF = 0.00325 (221/68016). AF 95% confidence interval is 0.0029. There are 0 homozygotes in GnomAd4. There are 170 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 13 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.9987C>T	p.Ser3329Ser	synonymous	Exon 68 of 93	NP_001193856.1
	DNAH8	NM_001371.4		c.9336C>T	p.Ser3112Ser	synonymous	Exon 67 of 92	NP_001362.2
	DNAH8-AS1	NR_038401.1		n.783-7387G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	ENST00000327475.11	TSL:5 MANE Select	c.9987C>T	p.Ser3329Ser	synonymous	Exon 68 of 93	ENSP00000333363.7
	DNAH8	ENST00000359357.7	TSL:2	c.9336C>T	p.Ser3112Ser	synonymous	Exon 66 of 91	ENSP00000352312.3
	DNAH8	ENST00000449981.6	TSL:5	c.9987C>T	p.Ser3329Ser	synonymous	Exon 67 of 82	ENSP00000415331.2

Frequencies

GnomAD3 genomes AF: 0.00225 AC: 342 AN: 152090 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00746

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00325

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00329 AC: 797 AN: 242030 AF XY: 0.00346

Gnomad AFR exome AF: 0.000445

Gnomad AMR exome AF: 0.000412

Gnomad ASJ exome AF: 0.00101

Gnomad EAS exome AF: 0.0000571

Gnomad FIN exome AF: 0.00878

Gnomad NFE exome AF: 0.00465

Gnomad OTH exome AF: 0.00291

GnomAD4 exome AF: 0.00272 AC: 3945 AN: 1452056 Hom.: 13 Cov.: 31 AF XY: 0.00268 AC XY: 1934 AN XY: 722300

African (AFR) AF: 0.000305 AC: 10 AN: 32768

American (AMR) AF: 0.000354 AC: 15 AN: 42332

Ashkenazi Jewish (ASJ) AF: 0.000694 AC: 18 AN: 25954

East Asian (EAS) AF: 0.0000256 AC: 1 AN: 39074

South Asian (SAS) AF: 0.00182 AC: 153 AN: 84258

European-Finnish (FIN) AF: 0.0101 AC: 540 AN: 53322

Middle Eastern (MID) AF: 0.000348 AC: 2 AN: 5744

European-Non Finnish (NFE) AF: 0.00277 AC: 3069 AN: 1108622

Other (OTH) AF: 0.00228 AC: 137 AN: 59982

GnomAD4 genome AF: 0.00225 AC: 342 AN: 152208 Hom.: 0 Cov.: 32 AF XY: 0.00228 AC XY: 170 AN XY: 74406

African (AFR) AF: 0.000530 AC: 22 AN: 41524

American (AMR) AF: 0.000523 AC: 8 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4820

European-Finnish (FIN) AF: 0.00746 AC: 79 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00325 AC: 221 AN: 68016

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.00309 Hom.: 1

Bravo AF: 0.00174

Asia WGS AF: 0.00144 AC: 5 AN: 3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Jan 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DNAH8: BP4, BP7

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	6.2
DANN	Benign	0.74
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs150857304; hg19: chr6-38883000; COSMIC: COSV107384996;