rs1542477

Variant names:

• chr2-84544443-C-T
• rs1542477
• NM_001370.2:c.873C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-84544443-C-T
• chr2-84544443-C-A
• chr2-84544443-C-G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001370.2(DNAH6):​c.873C>T​(p.Ser291Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.911 in 1,528,912 control chromosomes in the GnomAD database, including 640,892 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.82 (53456 hom., cov: 32)
  • Exomes 𝑓: 0.92 (587436 hom.)
• Consequence: DNAH6 NM_001370.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.457
• Publications: 12 publications found

Genes affected

DNAH6 (HGNC:2951): (dynein axonemal heavy chain 6) This gene belongs to the dynein family, whose members encode large proteins that are constituents of the microtubule-associated motor protein complex. This complex is composed of dynein heavy, intermediate and light chains, which can be axonemal or cytoplasmic. This protein is an axonemal dynein heavy chain. It is involved in producing force for ciliary beating by using energy from ATP hydrolysis. Mutations in this gene may cause primary ciliary dyskinesia (PCD) as well as heterotaxy. [provided by RefSeq, Jun 2016]

DNAH6 Gene-Disease associations (from GenCC):

• spermatogenic failure

  Inheritance: AR Classification: STRONG Submitted by: ClinGen
• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center
• primary ciliary dyskinesia

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 2-84544443-C-T is Benign according to our data. Variant chr2-84544443-C-T is described in ClinVar as Benign. ClinVar VariationId is 402733.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.457 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH6	NM_001370.2	MANE Select	c.873C>T	p.Ser291Ser	synonymous	Exon 5 of 77	NP_001361.1	Q9C0G6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH6	ENST00000389394.8	TSL:5 MANE Select	c.873C>T	p.Ser291Ser	synonymous	Exon 5 of 77	ENSP00000374045.3	Q9C0G6-1
	DNAH6	ENST00000494025.1	TSL:1	n.230-3845C>T		intron	N/A
	DNAH6	ENST00000476689.5	TSL:2	n.537-3845C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.818 AC: 124372 AN: 151980 Hom.: 53448 Cov.: 32

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.902

Gnomad AMR AF: 0.890

Gnomad ASJ AF: 0.936

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.890

Gnomad FIN AF: 0.955

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.933

Gnomad OTH AF: 0.847

GnomAD2 exomes AF: 0.911 AC: 140725 AN: 154432 AF XY: 0.914

Gnomad AFR exome AF: 0.509

Gnomad AMR exome AF: 0.937

Gnomad ASJ exome AF: 0.932

Gnomad EAS exome AF: 0.989

Gnomad FIN exome AF: 0.957

Gnomad NFE exome AF: 0.932

Gnomad OTH exome AF: 0.920

GnomAD4 exome AF: 0.921 AC: 1268318 AN: 1376814 Hom.: 587436 Cov.: 32 AF XY: 0.921 AC XY: 626734 AN XY: 680216

African (AFR) AF: 0.510 AC: 15949 AN: 31260

American (AMR) AF: 0.931 AC: 33212 AN: 35660

Ashkenazi Jewish (ASJ) AF: 0.934 AC: 23330 AN: 24988

East Asian (EAS) AF: 0.978 AC: 34709 AN: 35484

South Asian (SAS) AF: 0.890 AC: 69943 AN: 78590

European-Finnish (FIN) AF: 0.957 AC: 47020 AN: 49140

Middle Eastern (MID) AF: 0.869 AC: 4912 AN: 5654

European-Non Finnish (NFE) AF: 0.933 AC: 987710 AN: 1058806

Other (OTH) AF: 0.900 AC: 51533 AN: 57232

GnomAD4 genome AF: 0.818 AC: 124418 AN: 152098 Hom.: 53456 Cov.: 32 AF XY: 0.822 AC XY: 61129 AN XY: 74338

African (AFR) AF: 0.526 AC: 21782 AN: 41446

American (AMR) AF: 0.891 AC: 13604 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.936 AC: 3250 AN: 3472

East Asian (EAS) AF: 0.986 AC: 5110 AN: 5180

South Asian (SAS) AF: 0.890 AC: 4293 AN: 4824

European-Finnish (FIN) AF: 0.955 AC: 10133 AN: 10606

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.933 AC: 63391 AN: 67976

Other (OTH) AF: 0.848 AC: 1790 AN: 2112

Alfa AF: 0.874 Hom.: 27178

Bravo AF: 0.803

Asia WGS AF: 0.908 AC: 3150 AN: 3468

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	10
DANN	Benign	0.74
PhyloP100		0.46
Mutation Taster		=100/0	polymorphism (auto)

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: rs1542477; hg19: chr2-84771567; COSMIC: COSV108041474; COSMIC: COSV108041474;