rs778081949

Variant names:

• chr8-144513006-C-A
• rs778081949
• NM_004260.4:c.2596G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-144513006-C-A
• chr8-144513006-C-G
• chr8-144513006-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001413019.1(RECQL4):​c.2596G>T​(p.Gly866Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000494 in 1,418,276 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G866E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: RECQL4 NM_001413019.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.916
• Publications: 0 publications found

Genes affected

RECQL4 (HGNC:9949): (RecQ like helicase 4) The protein encoded by this gene is a DNA helicase that belongs to the RecQ helicase family. DNA helicases unwind double-stranded DNA into single-stranded DNAs and may modulate chromosome segregation. This gene is predominantly expressed in thymus and testis. Mutations in this gene are associated with Rothmund-Thomson, RAPADILINO and Baller-Gerold syndromes. [provided by RefSeq, Jan 2010]

RECQL4 Gene-Disease associations (from GenCC):

• Baller-Gerold syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Orphanet
• Rothmund-Thomson syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Rothmund-Thomson syndrome type 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, G2P
• osteosarcoma

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
• rapadilino syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp

ENSG00000265393 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001413019.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL4	NM_004260.4	MANE Select	c.2596G>T	p.Gly866Trp	missense	Exon 15 of 21	NP_004251.4
	RECQL4	NM_001413019.1		c.2596G>T	p.Gly866Trp	missense	Exon 15 of 20	NP_001399948.1
	RECQL4	NM_001413036.1		c.2596G>T	p.Gly866Trp	missense	Exon 15 of 21	NP_001399965.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL4	ENST00000617875.6	TSL:1 MANE Select	c.2596G>T	p.Gly866Trp	missense	Exon 15 of 21	ENSP00000482313.2
	RECQL4	ENST00000621189.4	TSL:1	c.1525G>T	p.Gly509Trp	missense	Exon 14 of 20	ENSP00000483145.1
	RECQL4	ENST00000971710.1		c.2503G>T	p.Gly835Trp	missense	Exon 15 of 21	ENSP00000641769.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000494 AC: 7 AN: 1418276 Hom.: 0 Cov.: 66 AF XY: 0.00000428 AC XY: 3 AN XY: 701634

African (AFR) AF: 0.00 AC: 0 AN: 32448

American (AMR) AF: 0.00 AC: 0 AN: 38038

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25424

East Asian (EAS) AF: 0.00 AC: 0 AN: 37176

South Asian (SAS) AF: 0.00 AC: 0 AN: 81118

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49006

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5720

European-Non Finnish (NFE) AF: 0.00000550 AC: 6 AN: 1090580

Other (OTH) AF: 0.0000170 AC: 1 AN: 58766

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	16
DANN	Benign	0.69
DEOGEN2	Benign	0.056	T
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.53	T
M_CAP	Uncertain	0.095	D
MetaRNN	Uncertain	0.58	D
MutationAssessor	Benign	1.8	L
PhyloP100		-0.92
PrimateAI	Benign	0.32	T
Sift4G	Uncertain	0.0040	D
Polyphen		0.98	D
Vest4		0.55
MVP		0.59
GERP RS		1.9
PromoterAI		-0.021	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.5
Varity_R		0.025
gMVP		0.44
Mutation Taster		=88/12	polymorphism

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: rs778081949; hg19: chr8-145738389;