rs2276293

Variant names:

• chr11-77206175-A-G
• rs2276293
• NM_000260.4:c.5715A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-77206175-A-G
• chr11-77206175-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000260.4(MYO7A):​c.5715A>G​(p.Lys1905Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 1,611,312 control chromosomes in the GnomAD database, including 200,746 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.56 (24425 hom., cov: 31)
  • Exomes 𝑓: 0.49 (176321 hom.)
• Consequence: MYO7A NM_000260.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:15
• Conservation: PhyloP100: 1.16
• Publications: 26 publications found

Genes affected

MYO7A (HGNC:7606): (myosin VIIA) This gene is a member of the myosin gene family. Myosins are mechanochemical proteins characterized by the presence of a motor domain, an actin-binding domain, a neck domain that interacts with other proteins, and a tail domain that serves as an anchor. This gene encodes an unconventional myosin with a very short tail. Defects in this gene are associated with the mouse shaker-1 phenotype and the human Usher syndrome 1B which are characterized by deafness, reduced vestibular function, and (in human) retinal degeneration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

MYO7A Gene-Disease associations (from GenCC):

• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive nonsyndromic hearing loss 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• Usher syndrome type 1

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Usher syndrome type 1B

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• autosomal dominant nonsyndromic hearing loss 11

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Usher syndrome type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 11-77206175-A-G is Benign according to our data. Variant chr11-77206175-A-G is described in ClinVar as Benign. ClinVar VariationId is 43296.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.16 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000260.4. 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
	MYO7A	NM_000260.4	MANE Select	c.5715A>G	p.Lys1905Lys	synonymous	Exon 41 of 49	NP_000251.3	Q13402-1
	MYO7A	NM_001127180.2		c.5601A>G	p.Lys1867Lys	synonymous	Exon 41 of 49	NP_001120652.1	Q13402-2
	MYO7A	NM_001369365.1		c.5568A>G	p.Lys1856Lys	synonymous	Exon 42 of 50	NP_001356294.1	Q13402-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO7A	ENST00000409709.9	TSL:1 MANE Select	c.5715A>G	p.Lys1905Lys	synonymous	Exon 41 of 49	ENSP00000386331.3	Q13402-1
	MYO7A	ENST00000458637.6	TSL:1	c.5601A>G	p.Lys1867Lys	synonymous	Exon 41 of 49	ENSP00000392185.2	Q13402-2
	MYO7A	ENST00000409619.6	TSL:1	c.5568A>G	p.Lys1856Lys	synonymous	Exon 42 of 50	ENSP00000386635.2	Q13402-8

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84647 AN: 151796 Hom.: 24373 Cov.: 31

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.540

GnomAD2 exomes AF: 0.516 AC: 127132 AN: 246242 AF XY: 0.502

Gnomad AFR exome AF: 0.706

Gnomad AMR exome AF: 0.641

Gnomad ASJ exome AF: 0.429

Gnomad EAS exome AF: 0.509

Gnomad FIN exome AF: 0.594

Gnomad NFE exome AF: 0.482

Gnomad OTH exome AF: 0.484

GnomAD4 exome AF: 0.488 AC: 711550 AN: 1459398 Hom.: 176321 Cov.: 39 AF XY: 0.483 AC XY: 350887 AN XY: 725886

African (AFR) AF: 0.706 AC: 23602 AN: 33442

American (AMR) AF: 0.634 AC: 28219 AN: 44496

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 10971 AN: 26098

East Asian (EAS) AF: 0.483 AC: 19151 AN: 39626

South Asian (SAS) AF: 0.396 AC: 34030 AN: 86008

European-Finnish (FIN) AF: 0.594 AC: 31611 AN: 53236

Middle Eastern (MID) AF: 0.442 AC: 2550 AN: 5766

European-Non Finnish (NFE) AF: 0.479 AC: 532348 AN: 1110448

Other (OTH) AF: 0.482 AC: 29068 AN: 60278

GnomAD4 genome AF: 0.558 AC: 84766 AN: 151914 Hom.: 24425 Cov.: 31 AF XY: 0.561 AC XY: 41613 AN XY: 74234

African (AFR) AF: 0.704 AC: 29183 AN: 41434

American (AMR) AF: 0.588 AC: 8980 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 1494 AN: 3472

East Asian (EAS) AF: 0.492 AC: 2529 AN: 5142

South Asian (SAS) AF: 0.380 AC: 1825 AN: 4800

European-Finnish (FIN) AF: 0.603 AC: 6373 AN: 10576

Middle Eastern (MID) AF: 0.493 AC: 144 AN: 292

European-Non Finnish (NFE) AF: 0.481 AC: 32648 AN: 67902

Other (OTH) AF: 0.540 AC: 1142 AN: 2114

Alfa AF: 0.508 Hom.: 36955

Bravo AF: 0.566

Asia WGS AF: 0.452 AC: 1570 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	3	not provided (3)
-	-	2	Autosomal dominant nonsyndromic hearing loss 11 (2)
-	-	2	Autosomal recessive nonsyndromic hearing loss 2 (2)
-	-	2	Usher syndrome type 1 (2)
-	-	1	Usher syndrome type 1B (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	6.7
DANN	Benign	0.59
PhyloP100		1.2
Mutation Taster		=99/1	polymorphism (auto)

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: rs2276293; hg19: chr11-76917220; COSMIC: COSV68683630; COSMIC: COSV68683630;