2-195897767-TAAAA-TAA

Position:

• chr2-195897767-TAAAA-TAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_018897.3(DNAH7):​c.4549-4_4549-3delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0286 in 1,116,596 control chromosomes in the GnomAD database, including 5 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0042 (5 hom., cov: 16)
  • Exomes 𝑓: 0.032 (0 hom.)
• Consequence: DNAH7 NM_018897.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH7	NM_018897.3	c.4549-4_4549-3delTT		splice_region_variant, intron_variant		ENST00000312428.11	NP_061720.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH7	ENST00000312428.11	c.4549-4_4549-3delTT		splice_region_variant, intron_variant		1	NM_018897.3	ENSP00000311273.6
DNAH7	ENST00000475293.1	n.5482-4_5482-3delTT		splice_region_variant, intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.00419 AC: 523 AN: 124956 Hom.: 5 Cov.: 16

Gnomad AFR AF: 0.0123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00233

Gnomad ASJ AF: 0.00101

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000534

Gnomad FIN AF: 0.00168

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000356

Gnomad OTH AF: 0.00357

GnomAD3 exomes AF: 0.0485 AC: 4517 AN: 93048 Hom.: 0 AF XY: 0.0494 AC XY: 2501 AN XY: 50580

Gnomad AFR exome AF: 0.100

Gnomad AMR exome AF: 0.0472

Gnomad ASJ exome AF: 0.0476

Gnomad EAS exome AF: 0.0280

Gnomad SAS exome AF: 0.0513

Gnomad FIN exome AF: 0.0240

Gnomad NFE exome AF: 0.0478

Gnomad OTH exome AF: 0.0504

GnomAD4 exome AF: 0.0317 AC: 31412 AN: 991630 Hom.: 0 AF XY: 0.0320 AC XY: 16037 AN XY: 501208

Gnomad4 AFR exome AF: 0.0827

Gnomad4 AMR exome AF: 0.0399

Gnomad4 ASJ exome AF: 0.0374

Gnomad4 EAS exome AF: 0.0162

Gnomad4 SAS exome AF: 0.0363

Gnomad4 FIN exome AF: 0.0243

Gnomad4 NFE exome AF: 0.0304

Gnomad4 OTH exome AF: 0.0335

GnomAD4 genome AF: 0.00419 AC: 523 AN: 124966 Hom.: 5 Cov.: 16 AF XY: 0.00429 AC XY: 257 AN XY: 59854

Gnomad4 AFR AF: 0.0123

Gnomad4 AMR AF: 0.00233

Gnomad4 ASJ AF: 0.00101

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000539

Gnomad4 FIN AF: 0.00168

Gnomad4 NFE AF: 0.000356

Gnomad4 OTH AF: 0.00355

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs61502519; hg19: chr2-196762491;