chr2-195897767-TAAA-T

Variant names:

• chr2-195897767-TAAA-T
• rs61502519
• NM_018897.3:c.4549-5_4549-3delTTT

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_018897.3(DNAH7):​c.4549-5_4549-3delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00238 in 1,138,928 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000024 (0 hom., cov: 16)
  • Exomes 𝑓: 0.0027 (0 hom.)
• Consequence: DNAH7 NM_018897.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.03

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00266 (2702/1013942) while in subpopulation AFR AF= 0.00641 (142/22170). AF 95% confidence interval is 0.00555. There are 0 homozygotes in gnomad4_exome. There are 1329 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH7	NM_018897.3	c.4549-5_4549-3delTTT		splice_region_variant, intron_variant	Intron 28 of 64	ENST00000312428.11	NP_061720.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH7	ENST00000312428.11	c.4549-5_4549-3delTTT		splice_region_variant, intron_variant	Intron 28 of 64	1	NM_018897.3	ENSP00000311273.6
DNAH7	ENST00000475293.1	n.5482-5_5482-3delTTT		splice_region_variant, intron_variant	Intron 1 of 2	1

Frequencies

GnomAD3 genomes AF: 0.0000240 AC: 3 AN: 124976 Hom.: 0 Cov.: 16

Gnomad AFR AF: 0.0000271

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000305

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00445 AC: 414 AN: 93048 Hom.: 0 AF XY: 0.00465 AC XY: 235 AN XY: 50580

Gnomad AFR exome AF: 0.00770

Gnomad AMR exome AF: 0.00525

Gnomad ASJ exome AF: 0.00497

Gnomad EAS exome AF: 0.00332

Gnomad SAS exome AF: 0.00566

Gnomad FIN exome AF: 0.00162

Gnomad NFE exome AF: 0.00396

Gnomad OTH exome AF: 0.00840

GnomAD4 exome AF: 0.00266 AC: 2702 AN: 1013942 Hom.: 0 AF XY: 0.00259 AC XY: 1329 AN XY: 512452

Gnomad4 AFR exome AF: 0.00641

Gnomad4 AMR exome AF: 0.00400

Gnomad4 ASJ exome AF: 0.00360

Gnomad4 EAS exome AF: 0.00115

Gnomad4 SAS exome AF: 0.00400

Gnomad4 FIN exome AF: 0.00159

Gnomad4 NFE exome AF: 0.00250

Gnomad4 OTH exome AF: 0.00285

GnomAD4 genome AF: 0.0000240 AC: 3 AN: 124986 Hom.: 0 Cov.: 16 AF XY: 0.00 AC XY: 0 AN XY: 59862

Gnomad4 AFR AF: 0.0000271

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000305

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

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;