2-195738062-A-T

Variant names:

• chr2-195738062-A-T
• rs80112322
• NM_018897.3:c.11934T>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 2P and 16B. PVS1_Moderate BP6_Very_Strong BS1 BS2

The NM_018897.3(DNAH7):​c.11934T>A​(p.Tyr3978*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00336 in 1,614,008 control chromosomes in the GnomAD database, including 16 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0023 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0035 (16 hom.)
• Consequence: DNAH7 NM_018897.3 stop_gained
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.16
• Publications: 11 publications found

Genes affected

DNAH7 (HGNC:18661): (dynein axonemal heavy chain 7) DNAH7 is a component of the inner dynein arm of ciliary axonemes (Zhang et al., 2002 [PubMed 11877439]).[supplied by OMIM, Mar 2008]

DNAH7 Gene-Disease associations (from GenCC):

• ciliary dyskinesia, primary, 50

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: LIMITED Submitted by: King Faisal Specialist Hospital and Research Center

LOC107985972 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0117 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• BP6: Variant 2-195738062-A-T is Benign according to our data. Variant chr2-195738062-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 715894.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00228 (348/152318) while in subpopulation NFE AF = 0.00388 (264/68028). AF 95% confidence interval is 0.0035. There are 0 homozygotes in GnomAd4. There are 150 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 16 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018897.3. 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
	DNAH7	NM_018897.3	MANE Select	c.11934T>A	p.Tyr3978*	stop_gained	Exon 65 of 65	NP_061720.2	Q8WXX0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH7	ENST00000312428.11	TSL:1 MANE Select	c.11934T>A	p.Tyr3978*	stop_gained	Exon 65 of 65	ENSP00000311273.6	Q8WXX0-1
	DNAH7	ENST00000409063.5	TSL:1	c.1383T>A	p.Tyr461*	stop_gained	Exon 10 of 10	ENSP00000386912.1	Q8WXX0-2
	DNAH7	ENST00000438565.1	TSL:3	c.*65T>A		3_prime_UTR	Exon 3 of 3	ENSP00000409732.1	H7C362

Frequencies

GnomAD3 genomes AF: 0.00229 AC: 348 AN: 152200 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000893

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.000982

Gnomad ASJ AF: 0.00518

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00388

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00230 AC: 573 AN: 249284 AF XY: 0.00209

Gnomad AFR exome AF: 0.00110

Gnomad AMR exome AF: 0.00188

Gnomad ASJ exome AF: 0.00526

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000464

Gnomad NFE exome AF: 0.00352

Gnomad OTH exome AF: 0.00380

GnomAD4 exome AF: 0.00347 AC: 5078 AN: 1461690 Hom.: 16 Cov.: 32 AF XY: 0.00339 AC XY: 2468 AN XY: 727154

African (AFR) AF: 0.000508 AC: 17 AN: 33476

American (AMR) AF: 0.00190 AC: 85 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00432 AC: 113 AN: 26132

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39696

South Asian (SAS) AF: 0.000185 AC: 16 AN: 86256

European-Finnish (FIN) AF: 0.000580 AC: 31 AN: 53418

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5762

European-Non Finnish (NFE) AF: 0.00419 AC: 4659 AN: 1111858

Other (OTH) AF: 0.00255 AC: 154 AN: 60376

GnomAD4 genome AF: 0.00228 AC: 348 AN: 152318 Hom.: 0 Cov.: 33 AF XY: 0.00201 AC XY: 150 AN XY: 74488

African (AFR) AF: 0.000890 AC: 37 AN: 41568

American (AMR) AF: 0.000981 AC: 15 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00518 AC: 18 AN: 3472

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10616

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

European-Non Finnish (NFE) AF: 0.00388 AC: 264 AN: 68028

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00303 Hom.: 1

Bravo AF: 0.00221

TwinsUK AF: 0.00351 AC: 13

ALSPAC AF: 0.00519 AC: 20

ESP6500AA AF: 0.000783 AC: 3

ESP6500EA AF: 0.00243 AC: 20

ExAC AF: 0.00245 AC: 296

EpiCase AF: 0.00349

EpiControl AF: 0.00284

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	DNAH7-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Pathogenic	0.46
CADD	Pathogenic	36
DANN	Uncertain	0.99
Eigen	Benign	0.047
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.70	D
PhyloP100		1.2
Vest4		0.24
GERP RS		-2.0
Mutation Taster		=143/57	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: rs80112322; hg19: chr2-196602786;